Methicillin-resistant Staphylococcus aureus (MRSA), one of the most common causes of infections, has been traditionally recognized as a nosocomial pathogen. However, in recent years, its epidemiology has radically changed, being now observed even more frequently in the community, and accounting for > 50% of staphylococcal infections in the US outpatient setting. Community-acquired (CA)-MRSA strains typically cause infections among otherwise healthy individuals, with risk factors differing from those of nosocomial MRSA. The clinical manifestations may range from a furuncle to life-threatening infections, such as necrotizing fasciitis and pneumonia. The antibiotic treatment of these infections may also differ because CA-MRSA strains often retain susceptibility to antimicrobials other than glycopeptides and newer agents. Moreover, the production of toxins, such as the Panton-Valentine leukocidin (PVL), should influence the antibiotic choice because in these cases the use of a combination therapy with antimicrobial agents able to decrease toxin production is suggested. There are still many unanswered key questions regarding the epidemiology, prevention, and treatment of CA-MRSA infections. This article reviews current knowledge of CA-MRSA.