1. The human immunodeficiency virus invades the central nervous system early after infection where it later gives rise to cognitive, motor, and behavioral manifestations in children and adults. 2. Ranging from mild impairments to frank dementia, CNS manifestations can be diagnosed and measured with standard neuropsychological test batteries. 3. Great strides have been made with treatment: CNS manifestations are treatable, as are depression, psychosis, and delirium which sometimes accompany HIV disease at different stages. 4. With startling advances in antiretroviral therapy and lower mortality, patients face a constellation of new concerns stemming from HIV's transformation to a more chronic disease. 5. There are many compelling research directions ahead, including the psychosocial impact of living with HIV as a chronic disease, the development of medications expressly targeted to the CNS, and basic research on neuropathogenesis, including trafficking of virus into the CNS.