Methicillin resistance, long recognized as characteristic of nosocomial Staphylococcus aureus, has increasingly been identified in community-acquired strains in the past 15 years. The genotypes of community-associated methicillin-resistant S. aureus (MRSA) are different from nosocomial strains, and unlike nosocomial strains, they have a distinctive methicillin-resistance chromosomal cassette (designated type IV), are usually susceptible to multiple classes of antimicrobials other than β-lactams, carry a distinctive virulence factor (the Panton-Valentine leukocidin), cause mainly skin and soft tissue infection and less frequently, necrotizing pneumonia, and involve predominantly children and young adults. Outbreaks have been reported in certain segments of the population (eg, football players, wrestlers, prison inmates, and native people) that often do not have the established risk factors for MRSA. However, these strains have also caused infections likely acquired in an institutional health care setting. Delay in starting appropriate antibiotic therapy for severe infections caused by MRSA can be life-threatening. This requires a reconsideration of the empiric choice of an anti-staphylococcal β-lactam for seriously ill patients with suspected community-associated S. aureus infections.