The human immunodeficiency virus (HIV), the cause of AIDS, has infected an estimated 33 million individuals worldwide. HIV is associated with immunodeficiency, neoplasia, and neurologic disease. The continuing evolution of the HIV epidemic has spurred an intense interest in a hitherto neglected area of medicine, neuroinfectious diseases and their consequences. This work has broad applications for the study of central nervous system (CNS) tumors, dementias, neuropathies, and CNS disease in other immunosuppressed individuals. HIV is neuroinvasive (can enter the CNS), neurotrophic (can live in neural tissues), and neurovirulent (causes disease of the nervous system). This article reviews the HIV-associated neurologic syndromes, which can be classified as primary HIV neurologic disease (in which HIV is both necessary and sufficient to cause the illness), secondary or opportunistic neurologic disease (in which HIV interacts with other pathogens, resulting in opportunistic infections and tumors), and treatment-related neurologic disease (such as immune reconstitution inflammatory syndrome).