Methicillin-resistant Staphylococcus aureus (MRSA) is well-recognised as a major cause of infection in the healthcare setting but, even more worryingly, is now emerging in the community. The glycopeptides—notably vancomycin—have traditionally been the mainstay of treatment of MRSA but overuse has led to the emergence of vancomycin-intermediate and vancomycin-resistant MRSA (VISA and VRSA, respectively). Although the mechanisms underlying vancomycin resistance are not yet fully understood, changes to the bacterial cell wall—the site of action of the glycopeptides—are believed to be key. Recent evidence also supports the transfer of genetic material among bacteria as contributing to the development of VRSA. Based on the cases identified to date, risk factors for the development of VRSA may include older age, compromised blood flow to the lower limbs, and the presence of chronic ulcers. The true extent of the problem, however, remains to be determined—it is likely that many cases of VISA and VRSA infection go undetected because of suboptimal screening programmes and possible limitations of automated and non-automated detection methods. Effective screening directed at those patients considered to be most at risk should therefore be a priority. Not surprisingly, the spread of MRSA from the hospital to the community setting, coupled with the emergence of VISA and VRSA, has become a major cause of concern among clinicians and microbiologists. The treatment options available for these infections are now severely compromised and thus new classes of antimicrobial agents effective against MRSA, VISA and VRSA are urgently required.