HIV-associated nephropathy (HIVAN) is the most well-known and aggressive kidney disease in HIV-1-infected patients. A variant of focal segmental glomerulosclerosis, it is characterized by the collapse of the glomerular tuft with podocyte hypertrophy/hyperplasia and foot process effacement, often with concurrent tubular microcystic dilation and tubulointerstitial nephritis. The disease has been intimately linked to the direct effect of HIV-1 on the kidney. It affects patients of African descent exclusively and is manifested by an acute decline in kidney function, most often in conjunction with high-grade proteinuria and uncontrolled HIV-1 infection. With the widespread use of highly active antiretroviral therapy (HAART), its prevalence is declining in Western countries. However, the epidemiology of the disease is not well defined in the poorest areas of the world, which bear a disproportionate share of the HIV-1 epidemic burden. Scientific evidence suggests that HAART can prevent the development of HIVAN. Furthermore, HAART, corticosteroids and inhibition of the renin-angiotensin axis are potentially helpful in delaying disease progression, as well as the need for renal replacement therapy.