Bacteremia caused by Staphylococcus aureus is a serious infection associated with high morbidity and mortality and often results in metastatic infections such as infective endocarditis, which have a negative impact on patient outcomes. We review the importance of the use of precise definitions of uncomplicated bacteremia and complicated bacteremia and present a case study to highlight the need for prolonged treatment and close monitoring of patients with risk factors for complications associated with S. aureus bacteremia. Traditionally, the treatment of choice for S. aureus bacteremia has depended to a large extent on the methicillin susceptibility of the pathogen. New antibiotics with proven efficacy against both susceptible and resistant strains are particularly attractive for empirical therapy. The antimicrobial agents that are currently available for use in the treatment of both methicillin-susceptible and methicillin-resistant S. aureus bacteremia and the scientific evidence that forms a basis for the use of these agents for this indication are reviewed.