Bloodstream infections are potentially life-threatening diseases. They can cause serious secondary infections, such as infective endocarditis and osteomyelitis, and may result in severe sepsis. One of the most critical determinants of survival is the induction of timely and effective antibiotic therapy. One of the leading causes of bloodstream infections is Staphylococcus aureus, with an increasing proportion of isolates being resistant to methicillin. Methicillin-resistant S. aureus (MRSA) is associated with greater morbidity and mortality rates than methicillin-sensitive S. aureus (MSSA). Standard-of-care antibiotic treatments for S. aureus bloodstream infections are limited by toxicity and/or differential efficacy against MRSA and MSSA, which makes the choice of empirical therapy difficult. New management strategies are required to address the challenges raised by S. aureus bloodstream infections and MRSA in particular. These may include the use of techniques that allow the early identification of complications arising from S. aureus bacteraemia, rapid pathogen identification to enable the administration of appropriate antibiotic therapy, and the identification of new drugs with novel modes of action that may circumvent antibiotic resistance and enable effective empirical treatment of both MSSA and MRSA infections.