Staphylococcus aureus is an opportunistic pathogen and the major causative agent of numerous hospital- and community-acquired infections. Multilocus sequence typing reveals a highly clonal structure for S. aureus. Although infrequently occurring across clonal complexes, homologous recombination still contributed to the evolution of this species over the long term. agr-mediated bacterial interference has divided S. aureus into four groups, which are independent of clonality and provide another view on S. aureus evolution. Genome sequencing of nine S. aureus strains has helped identify a number of virulence factors, but the key determinants for infection are still unknown. Comparison of commensal and pathogenic strains shows no difference in diversity or clonal assignments. Thus, phage dynamics and global transcriptome shifts are considered to be responsible for the pathogenicity. Community-acquired methicillin-resistant S. aureus (C-MRSA) is characterized by a short SCCmec and the presence of a Panton-Valentine leukocidin locus, but no studies have proven their exact biologic roles in C-MRSA infection, indicating the existence of other mechanisms for the genesis of C-MRSA.