Vancomycin earned notoriety for its tendency to cause nephrotoxicity shortly after it was introduced into practice, though the impurities responsible for historically significant rates of nephrotoxicity are of minimal concern today. Increasing usage of vancomycin has provided evidence that the drug itself can be nephrotoxic, but the exact mechanism by which this occurs has not been determined. Various studies have identified risk factors associated with development of vancomycin-associated nephrotoxicity, including total daily dose > 4 grams, trough levels > 20 mg/L, therapy exceeding 6 days, concurrent use of other nephrotoxic agents, preexisting renal disease, obesity, hypotensive episodes, and increasing severity of illness. Preventative strategies beyond risk assessment and therapeutic drug monitoring have shown little promise. Most cases of nephrotoxicity are reversible with discontinuation of vancomycin, but permanent renal damage can occur. This article is intended to serve as a practical review of vancomycin-associated nephrotoxicity, including historical context, risk factors, and common methods to evaluate and define renal dysfunction.