The deaths of neurons, astrocytes and endothelial cells have been described in patients with HIV (human immunodeficiency virus) dementia. HIV-1 does not infect neurons; instead, neurotoxic substances shed by infected glia and macrophages can induce a form of programmed cell death called apoptosis in neurons. These neurotoxins include the HIV-1 proteins Tat and gp120, as well as pro-inflammatory cytokines, chemokines, excitotoxins and proteases. In this article we review the evidence for apoptosis of various cell types within the brain of HIV-infected patients, and describe in vitro and in vivo experimental studies that have elucidated the mechanisms by which HIV causes apoptosis of brain cells.