Human immunodeficiency virus (HIV) infection is often complicated by the development of AIDS dementia complex (ADC). This article examines the typical and atypical presentations of ADC, along with aspects of the prevalence and natural history of the disorder. Salient aspects of the neuropathology, neurovirology, neuroimmunology, and pathogenesis are also considered. The intricacies of management of ADC, especially in the era of highly active antiretroviral therapy, are fully evaluated. Finally, this information is synthesized into an approach to the diagnosis of ADC in a particular patient.