The history and evolution of antimicrobial drugs, from their origins in ancient societies to the current challenges posed by multidrug-resistant microbes. The episode begins by outlining the historical use of antimicrobials, tracing their roots to ancient practices involving fermented beverages and herbal remedies. It then moves on to the discovery and development of modern antimicrobial drugs, highlighting key figures and pivotal discoveries like Ehrlich's "magic bullet" and Fleming's accidental discovery of penicillin. Mechanisms of drug resistance, emphasizing the role of natural selection and horizontal gene transfer in promoting the spread of resistance. Current challenges posed by multidrug-resistant microbes, including the emergence of "superbugs," and explore potential solutions to this critical global health concern, such as new drug discovery strategies and the development of compounds that inhibit resistance mechanisms.