The neuropsychiatric manifestations of HIV disease include neurobiologic and psychobiologic phenomena. The former consist of primary CNS complications caused directly by HIV, and include cognitive disorders (mild neurocognitive disorder and HIV-associated dementia) and other CNS diseases such as myelopathy and the demyelinating neuropathies; and secondary disorders (principally deliria) occasioned by opportunistic infections, neoplasms, cerebrovascular events, and the effects of metabolic derangements and medications. The latter (psychobiologic) phenomena reflect efforts to cope with various nodal, or transition points, in HIV disease; such points of transition include time of serostatus determination, adaptation to asymptomatic seropositivity, response to early medical symptomatology, and later transition to frank AIDS. Anxiety symptoms and various efforts to cope with anxiety (e.g., denial, anger, withdrawal, hypochondriacal preoccupation) all can punctuate these transition points. Additionally, there may be reactivation of long-standing psychopathology (e.g., depression) in seropositive individuals who tend to belong to a group that has an elevated prevalence of pre-infection psychiatric disorder. These interacting neurobiologic and psychobiologic phenomena pose challenges to the psychiatrist who must develop a good understanding of the medical aspects of HIV infection, as well as the neuropsychiatry of AIDS. In this way psychiatric physicians can play an important role in early identification of neuropsychiatric complications, assist the medical team to anticipate emotional and behavioral disturbances, and develop treatment plans that maximize our ability to help those with HIV infection achieve the best possible quality of life.