Human immunodeficiency virus (HIV) enters the nervous system in the first hours of infection and remains present throughout the infection. Over the past 15 years, much has been learned about the neurologic complications of HIV infection, as well as secondary complications due to the development of opportunistic infections and increased risk of malignant neoplasms associated with the immunodeficient state. The increased risk of previously rare neurologic complications such as cryptococcal meningitis, toxoplasma encephalitis, and progressive multifocal leukoencephalopathy has permitted refinement of therapeutic stratagems for the treatment of these complications. While these are important issues, the fundamental neurologic problem is understanding the pathophysiology of the HIV infection in the brain so as to optimally treat this critical manifestation of acquired immunodeficiency syndrome (AIDS). Clinical observations and formal trials are contributing to the increasing knowledge about HIV disease in the brain.