New methods for the chemical modification of clinically important glycopeptide antibiotics are reviewed. Special emphasis is placed on chemical modification of the domestic antibiotic eremomycin, which has a number of advantages over the clinically used antibiotics vancomycin and teichoplanin. The most promising methods for glycopeptide modification at the aromatic ring and carboxyl group of the seventh amino acid of the peptide core and also at the amino groups of the carbohydrate moiety are discussed in detail. The structure-activity relations in a series of glycopeptide derivatives are revealed. It is shown that the presence of lipophilic substituents of certain structures and sizes is mandatory for activity toward glycopeptide-resistant enterococci to be displayed. The possibility of dimerization and interaction of these derivatives with membrane components of the bacterial cell wall is discussed. The structures of the derivatives most active toward glycopeptide-resistant enterococci and meticillin-resistant staphylococci are presented.