Decades of overuse and misuse of antibiotics have turned the resistance problem into a crisis. Preventive and corrective measures are urgently needed. This article presents a broad overview of the status of antimicrobial resistance. Resistance in key bacterial pathogens such as enterococci, staphylococci, pneumococci, and gram-negative bacilli; resistance to fluoroquinolones, third-generation cephalosporins, and the carbapenems; and mechanisms of resistance are discussed. The article also reviews the adverse impact of resistance on outcomes for patients with nosocomial infections. Finally, a brief overview of how the medical community can face its moment of truth is presented.