Staphylococcus aureus bacteremia (SAB) is an urgent medical problem due to its growing frequency and its poor associated outcome. As healthcare delivery increasingly involves invasive procedures and implantable devices, the number of patients at risk for SAB and its complications is likely to grow. Compounding this problem is the growing prevalence of methicillin-resistant S. aureus (MRSA) and the dwindling efficacy of vancomycin, long the treatment of choice for this pathogen. Despite the recent availability of several new antibiotics for S. aureus, new strategies for treatment and prevention are required for this serious, common cause of human infection.