Why do we need a vaccine? Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of infection in hospitals and incidence is linked in the public’s mind with hospital cleanliness. In the UK, MRSA causes approximately 7000 cases of bacteremia every year, with a mortality rate of approximately 25%. It probably causes 10–20-times more infections that are not reported, predominantly wound infections and those associated with intravascular access devices. But MRSA is only the tip of the iceberg. The real problem is S. aureus itself, which causes another 11,000 bacteremias with only a slightly lower mortalilty rate. Again, an enormous number of unreported infections also occur. It is well documented that the UK has one of the highest incidences of MRSA per S. aureus infection in Europe (40%); however, it is difficult to know how to interpret this information since we don’t know the incidence of S. aureus infections in other countries. Ideally, S. aureus infections are treated with flucloxacillin, but MRSA are resistant and treated with vancomycin. The first cases of fully vancomycin-resistant MRSA have recently been described. Although several new antimicrobials have been released or are due for release, resistance is already described. Not only do we rely on antimicrobials for treatment, but we are heavily dependent on them for prophylaxis, so that as resistant strains evolve we expect to see infection rates increase. Recent high profile attempts to improve infection control strategies to reduce MRSA incidence in the UK have largely been ineffective. Not only is S. aureus a problem in hospitals, but MRSA strains carrying genes for the Panton–Valentine leukodicin (PVL) are spreading through healthy populations, particularly in the USA [1]. They cause increasing numbers of severe skin and soft tissue infections, as well as fatal hemolytic pneumonia and shock. High-risk groups are those in the military, sports teams, prisoners, intravenous drug users and children. A vaccine to S. aureus infection would therefore be a useful therapeutic and commercially very attractive. However, it is not obvious who should receive a vaccine, especially when tackling hospital infection. Heathcare workers may be a logical step, although this is unlikely to prevent spread of S. aureus via unwashed hands. Immunocompromised patients often respond poorly to vaccines. Colonized patients may be attractive targets, yet few hospitals routinely screen patients on admission to determine who are the carriers, and thus they are rarely offered prophylactic antibiotics that might be just as effective as a vaccine. Despite these limitations, several companies have invested heavily in S. aureus vaccine research.