Staphylococcus aureus is a versatile pathogen capable of causing a wide range of human diseases. However, the role of different virulence factors in the development of staphylococcal infections remains incompletely understood. Some clonal types are well equipped to cause disease across the globe, whereas others are facile at causing disease among community members. In this review, general aspects of staphylococcal pathogenesis are addressed, with emphasis on methicillin-resistant strains. Although methicillin-resistant S. aureus (MRSA) strains are not necessarily more virulent than methicillin-sensitive S. aureus strains, some MRSA strains contain factors or genetic backgrounds that may enhance their virulence or may enable them to cause particular clinical syndromes. We examine these pathogenic factors.