Vancomycin and other glycopeptide antibiotics are the current mainstay of therapy for infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, the high prevalence of MRSA has led to increased use of vancomycin in chronic and seriously ill patients and has resulted in the emergence of MRSA with reduced susceptibility to glycopeptides. Multiple MRSA phenotypes demonstrate reduced susceptibility to glycopeptides. According to the Clinical and Laboratory Standards Institute, vancomycin-intermediate S. aureus (VISA) are now those isolates with minimum inhibitory concentrations (MICs) between 4 microg/mL and 8 microg/mL, whilst heterogeneous VISA (hVISA) strains appear to be susceptible to vancomycin but contain a subpopulation of cells with reduced susceptibility to vancomycin (MICs > or = 4 microg/mL). At this time, MICs for these strains are reported to range between 1 microg/mL and 2 microg/mL. Vancomycin-resistant S. aureus (VRSA) are defined as those having MICs > or = 16 microg/mL. The detection of reduced susceptibility to vancomycin by routine susceptibility testing is unreliable and vancomycin non-susceptibility is most probably being underreported. Reports of reduced clinical efficacy associated with vancomycin MICs between 1 microg/mL and 2 microg/mL have been published. Patients most at risk of infection by hVISA, VISA and VRSA appear to be those with previous exposure to vancomycin. VRSA appears in the elderly and those with chronic leg or decubitus ulcers mainly containing vancomycin-resistant enterococci, which were probably the donor organism of the vanA gene to S. aureus. All MRSA strains recovered from patients whose infections do not respond to vancomycin treatment should be tested accurately for vancomycin susceptibility if these phenotypes are not to be missed. Treatment options for infections due to MRSA with reduced susceptibility to vancomycin are limited. Rapid identification of patients harbouring VRSA, VISA or hVISA as well as prompt isolation and adherence to infection control protocols are paramount in controlling the dissemination of these pathogens.