Apoptosis is a key event in biologic homeostasis with particular importance to the immune system. It is an active energy‐dependent process that is tightly regulated and controlled by a variety of signal transduction pathways. Apoptosis modulation plays a part in the pathogenesis of many human diseases, including HIV infection. Although multiple mechanisms may contribute to the decline in CD4 T‐lymphocyte numbers observed, apoptosis is a significant factor. Alterations in levels of apoptosis are observed in both directly infected and uninfected bystander cells and a variety of pathways of apoptosis induction have been implicated. Apoptosis induction is related to death receptor and mitochondrial‐induced pathways in specific circumstances. These events have been linked to individual HIV proteins and have been demonstrated to be altered by antiretroviral therapy.