The article by Franklin D. Lowy discusses the emergence and evolution of antimicrobial resistance in *Staphylococcus aureus*, a significant pathogen causing a wide range of infections. The widespread use of antibiotics, particularly in animal feed, and international travel have contributed to the spread of resistant strains. Despite increased understanding of molecular mechanisms, effective new drugs have not yet been developed, contrasting with the rapid progress in antiviral therapy. *S. aureus* is particularly concerning due to its virulence and adaptability, with multidrug resistance becoming the norm. The article reviews the historical development of resistant strains, their spread, and the molecular mechanisms of resistance to specific antibiotics, including penicillin, methicillin, quinolones, and vancomycin. It also explores potential new approaches and targets for therapeutic and preventive interventions, such as novel antimicrobial agents and vaccines. The increasing threat of multidrug-resistant *S. aureus* underscores the need for stricter infection control measures and the development of new strategies to combat this growing public health concern.The article by Franklin D. Lowy discusses the emergence and evolution of antimicrobial resistance in *Staphylococcus aureus*, a significant pathogen causing a wide range of infections. The widespread use of antibiotics, particularly in animal feed, and international travel have contributed to the spread of resistant strains. Despite increased understanding of molecular mechanisms, effective new drugs have not yet been developed, contrasting with the rapid progress in antiviral therapy. *S. aureus* is particularly concerning due to its virulence and adaptability, with multidrug resistance becoming the norm. The article reviews the historical development of resistant strains, their spread, and the molecular mechanisms of resistance to specific antibiotics, including penicillin, methicillin, quinolones, and vancomycin. It also explores potential new approaches and targets for therapeutic and preventive interventions, such as novel antimicrobial agents and vaccines. The increasing threat of multidrug-resistant *S. aureus* underscores the need for stricter infection control measures and the development of new strategies to combat this growing public health concern.