The first association between HIV-1 infection and kidney disease was made in 1984 and much has been learned over the past 20 years. In recent years, more effective therapies for HIV-1 infection and its associated opportunistic infections have led to improved patient survival. However, with prolonged survival, morbidity associated with renal disease has also increased. Among the multiple glomerulopathies that can affect patients with HIV, focal segmental glomerulosclerosis (FSGS) is most common and frequently leads to end-stage renal disease. Although the precise mechanisms of HIV-associated FSGS remain to be elucidated, it appears that host genetic susceptibility, direct infection of the renal epithelium, and toxicity of one or more viral accessory protein contribute. Therapy for HIV-associated FSGS includes control of blood pressure and the use of angiotensin antagonist therapy. A randomized trial of angiotensin receptor blocker will be initiated shortly. Drug-related nephropathies are also common, manifesting as acute renal failure, nephrolithiasis, and interstitial nephritis. Tenofovir, a newer nucleoside analogue, has recently been implicated in causing tubular toxicity, although the incidence is low. Appropriate screening for renal dysfunction can minimize the likelihood of progressive renal injury in all patients with HIV-1 infection.