Staphylococcus aureus is a virulent pathogen that is currently a major cause of community-acquired infections, as well as infections in hospitalized patients. Morbidity and mortality due to S. aureus infections, such as sepsis, osteomyelitis, septic arthritis and infective endocarditis, remain high despite the use of newer antibiotics. Of major concern, methicillin resistance in S. aureus isolates has increased dramatically worldwide, especially among nosocomial isolates; this phenotype may be associated with resistance to other antistaphylococcal compounds, including vancomycin. This increase in prevalence of multiantibiotic resistance in S. aureus is a major public health concern. Currently, there is an intense focus on the development of novel vaccines for the prevention of S. aureus infections in high-risk populations and on new antimicrobial classes for the therapy of established S. aureus infections.