Vancomycin is a key antibiotic in the management of severe Gram-positive infections. Recent emergence of methicillin-resistant staphylococcal strains with reduced susceptibility to vancomycin has prompted internists to administer high-dose treatment to achieve trough levels of 15 to 20 mg/l. Such high doses might be causative in nephrotoxicity. The risk further increases in patients who are critically ill and are on vasopressor support and/or concomitant nephrotoxic agents, with baseline deranged renal function, undergoing prolonged duration of therapy and are obese. However, data are insufficient to recommend the superiority of continuous infusion regimens as compared with intermittent dosing. This review discusses the literature pertaining to vancomycin nephrotoxicity.