HIV-1 infection causes the depletion of CD4 T cells, which results in AIDS. There are numerous potential mechanisms by which this cell death can occur, and a majority of the molecular mechanisms involve the mitochondria. Furthermore, current HIV therapies also have an impact on mitochondrial stability. The alteration in apoptotic homeostasis induced by HIV, HIV proteins, the host response to HIV infection and/or HIV therapies either promote apoptosis or inhibit apoptotic signals depending on the cellular context. Latent HIV reservoirs prevent the eradication of the virus because these cells are resistant to apoptosis: a change potentially induced at the level of the mitochondria. Many of the novel treatment strategies aimed at eradicating the virus involve alterations of mitochondrial regulation of apoptosis. (C) 2004 Elsevier B.V. and Mitochondria Research Society. All rights reserved.