It would be difficult to envision the practice of infectious diseases over the past 20 years without the availability of the glycopeptide antibiotics. The two agents currently in clinical use, vancomycin and teicoplanin, have proven remarkably versatile in many common applications. Several attributes of these agents account for this favourable profile: (i) their broad spectrum of activity against Gram-positive bacteria, including strains resistant to many other antimicrobials; (ii) their favourable pharmacokinetic properties that allow the once- or twice-daily dosing regimens that have made out-of-hospital therapy possible; and (iii) their generally good safety profiles which, along with their structural dissimilarity to beta-lactam and other antimicrobials, permits their use in many patients who are intolerant of other antibiotic regimens. It is not entirely surprising, therefore, that despite more than 40 years of clinical use and the interim appearance of bacterial strains resistant to this drug class, there remains continued interest in the development of newer members of the glycopeptide antibiotic class. This paper is intended to provide a global overview of the efficacy and safety of glycopeptide antibiotics currently in use, as background to understanding the need for and potential roles of new agents of this class.