The prevalence of MRSA in the nosocomial setting has been well studied, and its control remains a challenge for infection control professionals. Complicating this problem is the increasing number of reports on the spread of community-acquired MRSA (CA-MRSA). CA-MRSA strains differ from hospital-acquired MRSA (HA-MRSA) strains in that they are generally susceptible to most antibiotics. These strains share the presence of staphylococcal cassette chromosome mec (SCCmec) type IV in their genomes, are frequently virulent, and predominantly cause skin and soft tissue infections. The genome sequence of the prototypic CA-MRSA strain, MW2, revealed the presence of additional virulence factors not commonly present in other S. aureus strains. We determined the genetic relatedness of 30 geographically diverse CA-MRSA isolates clustered based on SCCmec type IV by sequence analysis of the polymorphic repeat region of the protein A gene (spa typing). These results indicated that most strains shared a common spa type (131), identical to MW2. Because this group tends to infect healthy individuals with no known risk factors for nosocomial acquisition of MRSA, we refer to it as CA-MRSA without risk factors. A second group, CA-MRSA with risk factors, consists of two related genotypes, spa types 1 and 7, which differ by one nucleotide change. These strains have caused severe infections in HIV-positive patients in Los Angeles and New York. Although CA-MRSA strains share genetic determinants, they are not clonal but rather are derived from different genetic backgrounds. The genetic characteristics and the epidemiology of CA-MRSA with and without risk factors are discussed.