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 proinflammatory 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 describein vitro andin vivo experimental studies that have elucidated the mechanisms by which HIV causes apoptosis of brain cells.