Glycopeptide antibiotics have become the last bastion for the treatment of multidrug-resistant Gram-positive hospital pathogens, the two main ones being methicillin-resistant S. aureus and enterococci. However, in addition to the emergence of vancomycin resistance in enterococci, certain staphylococcal strains with low-level resistance to glycopeptides have increasingly been isolated from clinical specimens. This review focuses on mechanisms of resistance, epidemiology, control measures and therapeutic Options for these Staphylococci.