Infections due to Gram-positive bacteria have become an increasing problem in the ICU. Furthermore, multidrug resistance among Gram-positive pathogens is increasingly recognized. Empirical therapy with antibiotic regimens that are effective against Gram-positive pathogens is often required in the ICU. Many critically ill patients in the ICU have multiorgan system failure, including acute renal failure, which further impedes optimal antimicrobial therapy. In this communication, the use of glycopeptides in the ICU is briefly reviewed, and the occurrence of associated nephrotoxicity during therapy with vancomycin or teicoplanin, alone or in combination with an aminoglycoside, is examined. Finally, existing recommendations regarding the dose regimens of these agents in patients with renal impairment are evaluated, and guide-lines for optimizing glycopeptide therapy through improved pharmacokinetic monitoring are presented.