Since 1984, human immunodeficiency virus-associated nephropathy has been established as a clinical entity that presents with nephrotic syndrome and progressive kidney failure. The pathological description is usually consistent with a collapsing form of focal segmental glomerulosclerosis. Podocytes and renal tubular cells have been proposed as a reservoir for the human immunodeficiency virus. This nephropathy is the third leading cause of end-stage renal disease in the population of African descent. It is documented that highly active antiretroviral therapy (HAART) successfully reverses or at least controls nephropathy in HIV-positive patients. The success of the treatment of HIV nephropathy now poses 2 problems to nephrologists: (1) an increased population of HIV-positive patients with chronic kidney disease not yet on dialysis and (2) potential nephrotoxicity of antiretroviral medications as well as medications used to treat opportunistic infections. HAART is defined by the combination of 2 reverse transcriptase inhibitors with a protease inhibitor or 3 reverse-transcriptase inhibitors. Many of these antiretrovirals have well-defined nephrotoxic effects. The objective of this text is to review data pertaining to some of the most common antiretrovirals (ARTs) and include information regarding nephrotoxicity of the medications frequently used to combat opportunistic infections. ARTs included in the review are (1) nucleoside reverse-transcriptase inhibitors (zidovudine and didanosine), (2) nucleotide reverse transcriptase inhibitors (adefovir and tenofovir), (3) the protease inhibitors (indinavir and saquinavir), and (4) the HIV fusion inhibitors.