The a16z Show

Mark Cuban thinks AI could transform healthcare, but it won’t fix opaque prices and broken incentives on its own. His starting point for employers: run every benefits contract through AI and ask where you’re getting ripped off.

Mark joins a16z General Partner Julie Yoo and Erik Torenberg to discuss what he’s learned building Cost Plus Drugs, why trust is its core product, and how greater transparency could put pressure on healthcare costs.

They also explore where AI can help, what personalized medicine could look like, how the role of doctors may change, and why Mark believes founders should use AI to learn, not as an excuse to stop thinking.

Resources:

Follow Mark Cuban on X: https://x.com/mcuban 

Follow Julie Yoo: https://x.com/julesyoo 

Mark Cuban Cost Plus Drug Company: https://costplusdrugs.com/

Cost Plus Wellness: https://costpluswellness.com/

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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.

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What should school look like if AI can help students learn dramatically faster? Alpha School founder Joe Liemandt argues the answer isn’t to fill the extra time with more academics, but to redesign school around the skills traditional classrooms struggle to teach: agency, teamwork, entrepreneurship, communication, and doing hard things.

Joe joins Erik Torenberg and Horowitz and Andreessen Academy co-founder Gagan Biyani to discuss Alpha’s model, where students spend two hours a day on core academics and the rest developing real-world skills through projects. They explore what that approach can teach higher education, why motivation may matter more than curriculum, and how HAA is applying similar principles to college-age students by putting building, relationships, and real-world experience at the center of the learning experience. 

They also discuss what parents need to believe before choosing a new educational model, why Joe expects AI to drive an explosion in entrepreneurship, and why the most important question for students may not be which field is safest from AI, but what they care enough about to build. 

Resources:

Learn more about Horowitz and Andreessen Academy: https://www.theacademysf.com/ 

Learn more about Alpha School: https://alpha.school/joe-liemandt-and-the-future-of-education/ 

Follow Joe Liemandt on X: https://x.com/jliemandt 

Follow Gagan Biyani: on X https://x.com/gaganbiyani 

Follow Erik Torenberg on X: https://x.com/eriktorenberg

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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.

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AI agents are approaching a point where they can use computers faster than expert humans, turning the user interface itself into a universal way for AI to interact with software. OpenAI’s Ari Weinstein and James Sun argue that computer use is now entering its scaling moment, as better models, faster execution, and stronger safety controls make agents practical for more consumer and enterprise work.

Ari and James join a16z’s Seema Amble and Fabrizio Serafini to explain how computer-using agents are already navigating legacy ERPs, reconciling financial data, handling procurement, and operating software without APIs or custom integrations. They also discuss why the harness around the model can matter as much as model intelligence, how enterprises can set deterministic guardrails around agent behavior, and why computer use could simultaneously extend the life of legacy software and accelerate the arrival of new AI-native applications. 

Looking ahead, they make the case for a more proactive and fluid relationship with computers, where agents work in the background, collaborate with users in real time, and increasingly adapt to us rather than requiring us to learn how to use them.

Resources:

Follow Seema Amble on X: https://x.com/seema_amble 

Follow Fabrizio Serafini on X: https://x.com/fabserafini 

Follow Ari Weinstein on X: https://x.com/AriX 

Follow James Sun on X: https://x.com/JamesZmSun 

Related a16z research from Seema Amble and Fabrizio Serafini: Can Agents Use a Computer Yet? We’ve Got the Data

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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.

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Can a 10-person startup outperform a company with hundreds of employees? Box CEO Aaron Levie argues AI agents are giving small teams a level of leverage that simply wasn't economically possible before, creating a window for startups to outrun incumbents.

In this episode of Speedrun Office Hours, Aaron explains why founders are shifting from doing the work themselves to orchestrating agents, and why that puts a new premium on strategy, taste, and knowing exactly what to build. He makes the case that nearly every industry and job function could support specialized AI agents, potentially creating hundreds of new billion-dollar companies.

They also discuss why enterprise AI may capture much of the next wave of model improvements, how dramatically cheaper AI labor could unlock demand that doesn't exist today, and one thing Aaron thinks AI won't change: distribution. If you build it, they still won't necessarily come. 

Resources:

Watch the original Speedrun Office Hours episode: https://www.youtube.com/watch?v=wZ1joGIUyK8

Learn more about Speedrun: https://speedrun.a16z.com/

Follow Speedrun on X: https://x.com/speedrun

Follow Aaron Levie on X: https://x.com/levie

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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.

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What does it take to build a company when AI is changing the rules this quickly? Ben Horowitz argues that technology may make companies easier to start, but the hardest parts of entrepreneurship, making decisions under uncertainty, building momentum, and managing your own doubts, aren't going away.

Speedrun's Andrew Chen sits down with Ben to discuss why AI feels different from previous technology shifts, whether billion-dollar companies can be built with tiny teams, and why Ben thinks the application itself may eventually become less important as agents work directly against data.

They also get into defensibility in AI, what founders should look for in an investor, how venture capital is changing, and why the best entrepreneurs aren't defined by a lack of weaknesses, but by having a strength or insight that's genuinely exceptional. 

Resources:

Follow Ben Horowitz on X: https://x.com/bhorowitz

Follow Andrew Chen on X: https://x.com/andrewchen

Learn more about Speedrun: https://speedrun.a16z.com/apply

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Amazon expects to spend roughly $220 billion in CapEx in 2026, yet CEO Andy Jassy says the company is still leaving meaningful AI demand on the table.** He believes the buildout could ultimately help make AWS a $1 trillion annual run-rate business.

Andy joins a16z co-founder Ben Horowitz and Erik Torenberg to discuss why AI demand is growing so quickly, how Amazon decides how much infrastructure to build, and why lower inference costs could unlock broader enterprise adoption.

They also discuss how AI is reshaping Amazon itself, from smaller teams building products faster to reimagining Alexa, and why Andy sees cybersecurity, human judgment, and critical thinking as increasingly important in the AI era.

Resources:

Follow Andy Jassy on X: https://x.com/ajassy 

Follow Ben Horowitz on X: https://x.com/bhorowitz

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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.

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a16z is expanding a16z crypto into a16z Frontier, a broader mandate to back founders building at the edges of what's possible. Chris Dixon joins Marc Andreessen, Ben Horowitz, and Erik Torenberg to explain why founders should increasingly ask not “is this too ambitious?” but “is this ambitious enough?” — and how AI could pull decades of technological progress forward across hardware, robotics, entertainment, science, and entirely new forms of media.

They also explore the coming internet of AI agents, why open source matters as AI becomes more powerful, and why some of the most important companies of the next decade may combine technologies and business models that previously belonged in separate categories.

Resources: 

Follow Chris Dixon on X: https://x.com/cdixon
Follow Marc Andreessen on X: https://x.com/pmarca
Follow Ben Horowitz on X: https://x.com/bhorowitz
 

Learn more about a16z Frontier: 
https://a16zfrontier.com
https://a16zfrontier.substack.com
https://x.com/a16zfrontier

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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see http://a16z.com/disclosures.

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AI agents can reason over enormous amounts of information, but much of the world’s actual work is still trapped in PDFs, spreadsheets, scans, and other formats that models struggle to reliably understand. Reducto co-founder and CEO Adit Abraham argues that solving this document layer is essential if agents are going to take on consequential work in healthcare, legal, finance, and insurance.

Adit joins a16z General Partner Jennifer Li to explain why traditional OCR breaks down on messy real-world documents, how Reducto combines vision-language models with specialized infrastructure to reach high accuracy without sacrificing cost or latency, and why frontier models can silently drop information on long extraction tasks. Reducto now processes billions of pages each month, including its seven billionth page the morning of the recording. 

They also discuss Reducto’s R1 model, agents that can review and correct their own document extraction, and the company’s push beyond simply reading files toward letting agents reliably work with and edit them. Underneath it all is a higher-stakes problem: when a misread word can affect a healthcare claim or financial decision, getting the input right matters just as much as making the model smarter.

Resources:

Learn more about Reducto: https://reducto.ai

Follow Adit Abraham on X: https://x.com/aditabrm 

Follow Jennifer Li on X: https://x.com/JenniferHli

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More than 300 million people use ChatGPT for health and wellness questions each week. OpenAI’s Karan Singhal thinks that’s only the beginning: the longer-term goal is AI that can help people navigate their health proactively, while making trustworthy medical intelligence dramatically more accessible.

Karan joins a16z Partner Jay Rughani to explain why OpenAI trains healthcare expertise directly into its general-purpose frontier models, how it works with hundreds of medical experts to evaluate safety and disagreement, and why the company sees AI as a complement to doctors rather than a replacement for medical care. They also discuss integrations with Epic, AI copilots for clinicians, and what happens as personal agents begin navigating appointments, health records, and other fragmented parts of the healthcare system.

Looking further ahead, Karan makes the case that the cost of medical intelligence could continue to fall dramatically, allowing AI to act as a safety net for patients and clinicians, surface insights from years of health data, and potentially accelerate the discovery and validation of new treatments.

Resources:

Follow Karan Singhal on X: https://x.com/thekaransinghal 

Follow Jay Rughani on X: https://x.com/JayRughani 

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Why hasn't AI transformed everyday work as quickly as coding? Town CEO Jean-Denis Greze argues the bottleneck isn't intelligence, but making AI useful to people who don't have the time or technical skills to build their own automations.

Jean-Denis joins a16z General Partner Alex Rampell to share why he pivoted Town from tax software to a personal AI assistant built around email, calendars, and the workflows that run businesses. They discuss why consumer-grade experiences may win in enterprise AI, how Town discovers and automates tasks users wouldn't think to delegate, and why model neutrality and data ownership matter as AI labs increasingly compete with application companies.

They also explore what happens when agents begin acting on our behalf, from managing everyday work to shopping and commerce, and why the next generation of software may need to adapt to each user rather than the other way around.

Resources:

Follow Alex Rampell on X: https://x.com/arampell

Follow Jean-Denis Greze: https://x.com/jgreze

Learn more about Town: https://town.com

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Please note that the content here is for informational purposes only; should NOT be taken as legal, business, tax, or investment advice or be used to evaluate any investment or security; and is not directed at any investors or potential investors in any a16z fund. a16z and its affiliates may maintain investments in the companies discussed. For more details please see a16z.com/disclosures.

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