HIV-Dementia (HIV-D) is an important cause of dementia worldwide. Since the introduction of highly active retroviral therapy, the prevalence of HIV-D has decreased significantly but the proportion of those patients with CD4 at the higher range is increasing. HIV-associated minor cognitive impairment precedes the dementia. The latter is characterized by cognitive, behavioral and motor deficits. Neurological assessment, brain imaging, cerebrospinal fluid analysis and immunologic parameters are important diagnostic tools. Neuropathological data show inflammation and atrophy. The virus attacks brain astrocytes and neurons directly or indirectly by activation of macrophages. HIV-D is therefore an immunologic, inflammatory, and neurodegenerative disease. In the future, drugs will block cell-cell signaling or apoptosis.