In this episode, we examine phenobarbital monotherapy as an emerging approach to managing alcohol withdrawal syndrome. We discuss the advantages of phenobarbital over traditional benzodiazepine-based regimens, including more predictable pharmacokinetics, a wider therapeutic index, and broader neurological effects. Topics include accurate diagnosis, the benefits of phenobarbital’s long half-life for sustained symptom control and auto-tapering, and its potential to reduce intubation rates and complications. We also address contraindications and practical considerations for implementing a phenobarbital-first strategy in clinical practice.