Highly active antiretroviral therapy (HAART) is effective in suppressing systemic human immunodeficiency virus (HIV) viral load and has decreased mortality rates and the incidence of systemic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS). Multiple studies now suggest that the incidence rates of HIV-associated neurological disease and central nervous system (CNS) opportunistic infections also are decreasing. Since the introduction of HAART in 1996, the incidence of HIV dementia has decreased by approximately 50%. The mean CD4 cell count for new cases of HIV dementia is increasing, but it remains as a complication of moderate-advanced immunosuppression. The incidence of HIV-associated distal sensory polyneuropathy has decreased, although the incidence of antiretroviral drug-induced toxic neuropathy has increased. However, as patients with AIDS live longer as a result of HAART, the prevalence of peripheral neuropathy in HIV-seropositive patients may be increasing. The incidence rates of CNS opportunistic infections (cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy) and primary CNS lymphoma have decreased since the introduction of HAART. As patients develop increasing resistance mutations to antiretroviral drugs and with subsequent decline in CD4 cell counts, in the near future, the incidence of HIV-associated neurological disease may begin to rise.