HIV-1 infection is a worldwide pandemic, with an estimate of one to two million children infected by the end of the decade. The neurologic manifestations of primary HIV-1 infection in children are a major cause of morbidity and contribute to the fatal outcome in this condition. In the United States, HIV-1 is the most frequent cause of dementia in young adults. Because antiretroviral therapies and treatment for opportunistic infections have lengthened the survival time but not eradicated the virus from the central nervous system, it is likely that the incidence of neurologic dysfunction, including HIV-1 dementia, will increase. Available evidence suggests that the HIV-1 virus does not productively infect neurons but rather induces programmed cell death (apoptosis) in neurons by production of neurotoxic factors, including cytokines, phospholipid mediators, and eicosanoids, and HIV-1 gene products from HIV-1-infected macrophages in the brain. Understanding the mechanisms involved in neuronal cell injury and death may lead to new therapeutic interventions for the neurologic dysfunction associated with HIV-1 infection of the developing central nervous system.