Staphylococcus aureus is a pathogen that has caused human disease for centuries, and despite efforts to control it via modern antibiotics, this organism has persisted and continues to cause major clinical problems throughout the world. A remarkably versatile pathogen, it has virulence mechanisms that enable it to cause a broad variety of serious infections in man, and it has the ability to acquire new exogenous genes, which make it possible for it to adapt to a variety of changing environmental conditions and to modulate its pathogenicity. It can establish a symptomatic carriage that permits widespread dissemination. It has shown a remarkable ability to develop resistance to the major antibiotics directed against it including the penicillins. The development of methicillin resistance in staphylococci has resulted in organisms that continue to plague patients in institutionalized settings and elsewhere. More recently, there has been a worldwide outbreak (currently most prominent in the United States) of infections due to community-associated methicillin-resistant staphylococci. The factors that have made it possible for this to occur are defined in this article.