Vancomycin resistance in Staphylococcus aureus has recently emerged as an important clinical problem with implications for laboratory detection and clinical management of patients infected with resistant strains. To date, low-level vancomycin resistance in the form of vancomycin-intermediate S. aureus (VISA) and heterogenous vancomycin-intermediate S. aureus (hVISA) have been more common, with only four cases of true vancomycin resistant S. aureus (VRSA) reported. This article reviews current knowledge about the epidemiology, clinical manifestations and optimal management of hVISA and VISA infections. VISA and hVISA have now been reported from many countries, and these strains tend to occur in patients with significant comorbidities and previous antibiotic exposure. Despite the difficulties in laboratory detection, there are increasing data linking VISA and hVISA to failure of glycopeptide antimicrobial therapy. Aggressive surgical intervention and non-glycopeptide-based antimicrobial therapy appears to improve outcomes for patients infected with these low-level vancomycin-resistant strains. Clinicians and diagnostic laboratories need to be aware of VISA and hVISA as a clinical problem, and consider aggressive surgical debridement and non-glycopeptide-based therapy where infections with such strains are suspected or proven.