Antiretroviral therapy (ART) has made a significant impact on the morbidity and mortality of patients with HIV infection. However, many of these agents have nephrotoxic potential and are implicated in causing both acute and chronic kidney disease. Safely employing these medications requires a thorough understanding of risk factors that predispose to kidney injury, which include both patient-related characteristics as well drug-related factors. Acute tubular toxicity, crystal nephropathy, and acute interstitial nephritis are among the common renal manifestations of these drugs. Adefovir and tenofovir are associated with tubular toxicity. Crystalluria, crystal nephropathy and nephrolithiasis have been established with indinavir. Acute interstitial nephritis, although not common among antiretroviral agents, is seen with indinavir and atazanavir in these immunocompromised patients. Rarely, enfuvirtide may promote a glomerulopathy. Frequent exposure to other nephrotoxic non-antiretroviral drugs also contributes to kidney disease. Identification and reversal of potentially modifiable risk factors prior to drug administration is important to limiting kidney injury. Recognition of drug-related nephrotoxicity will promote earlier resolution of acute kidney injury and reduce the development of chronic kidney disease.