Direct effects of HIV-1 infection on the kidney combine with immune and genetic factors, comorbidities, coinfections, and medication toxicities to induce a spectrum of kidney disorders in HIV disease. The most dramatic of these, HIV-associated nephropathy (HIVAN), emerges almost exclusively in persons of African descent and is associated with rapid progression to end-stage renal disease in the absence of antiretroviral therapy (ART). ART modifies the natural history of HIVAN, but the renal benefits of ART may not be limited to HIVAN. ART is often under prescribed or incorrectly dosed in persons with kidney disease. Vigilant attention to renal function and an understanding of the complex associations involving the kidneys are necessary for optimal care of these patients.