Opportunistic infections of the central nervous system (CNS) are common complications of advanced immunodeficiency in individuals with human immunodeficiency virus type 1 (HIV-1) infection. Neurological disease is the first manifestation of acquired immunodeficiency syndrome (AIDS) in 10% to 20% of symptomatic HIV-1 infection. Prompt diagnosis and treatment of such disorders is critical. Also, in the era of highly active antiretroviral therapy (HAART), these disease states have changed in presentation and epidemiology. Therefore, we review the epidemiology, pathogenesis, clinical features, diagnosis, and management of five common central nervous system disorders in individuals with HIV-1 infection: toxoplasma encephalitis, primary central nervous system lymphoma, cryptococcal meningitis, cytomegalovirus encephalitis, and progressive multifocal leukoencephalopathy.