Methicillin-resistant Staphylococcus aureus (MRSA) isolates came into existence soon after the introduction of methicillin. Historically, MRSA isolates have been associated with nosocomial infections and rapidly developed resistance to multiple drug classes. However, in recent years, different strains with unique phenotypes have emerged in the community, and the reservoir of community-associated MRSA is rapidly expanding. Community-associated pathogens are likely to cause life-threatening systemic infections, especially in children and elderly individuals, and may also cause serious skin and soft-tissue infections in healthy individuals. Compared with nosocomial strains, community-associated MRSA isolates are associated with increased virulence and currently are more likely to be susceptible to a variety of antibiotics. The epidemiological and microbiological differences between community-associated and nosocomial MRSA infections necessitate different strategies to prevent and treat the 2 types of infections. Vancomycin nonsusceptibility in S. aureus is on the increase, further complicating therapy.