The emergence of Staphylococcus aureus resistant to vancomycin has caused considerable concern. Such strains are currently rare, although they have been isolated from many areas of the world. Considerable controversy surrounds strains of S. aureus displaying heterogeneous resistance to vancomycin regarding their definition and methods for detection. This has led to considerable variance in estimates of prevalence (0–1.3%–20% in Japan) and has hindered efforts to define the clinical relevance of these strains. The mechanism of resistance involves a complex reorganization of cell wall metabolism, leading to a grossly thickened cell wall with reduced peptidoglycan cross-linking. There may be many different ways in which strains achieve this endpoint. Current knowledge and theories are summarized.