Staphylococcus aureus is among the leading causes of community-acquired as well as healthcare-associated and hospital-acquired bacteremia and endocarditis. The purpose of this review was to analyze most recent data relevant to the clinical management of S. aureus bacteremia (SAB) and endocarditis. Population-based studies have shown that the incidence of SAB has not decreased in the last years and that healthcare-associated and nosocomial cases continue to account for at least half of SAB. In some areas where methicillin-resistant S. aureus (MRSA) now has become common, MRSA strains with reduced vancomycin susceptibility may have emerged and account for a significant proportion. These strains increase the likelihood of treatment failures, though overall outcomes may often be similarly poor in drug-susceptible S. aureus, which must not be neglected as a pathogen causing potentially lethal infection. Many aspects of drug therapy such as continuous versus intermittent infusion of antibiotics or combination therapy continue to be discussed controversially. Few major progresses in the clinical management have been made in the last few years, but there is evidence that the case fatality can be modestly reduced by efforts focussed on sustained high-quality clinical management. SAB remains a serious, potentially lethal infection, which is too often nosocomial and healthcare-associated. A threat has been the increasing drug resistance of S. aureus seen in many parts of the world and spreading among community isolates. Improved outcomes with new drugs have not been shown convincingly. Large clinical trials assessing the benefits of combination therapies are needed.