AIDS dementia complex is a relatively recently discovered source of cognitive and motor decline, clearly linked to CNS infection by HIV. While this condition is generally subacutely progressive, and leads to death in a short time-span in untreated patients, improvement in function and prognosis may be achieved by application of highly active antiretroviral therapy. Although this therapy is essential, it may also be necessary in the long term to provide additional neuroprotection, blocking secondary mechanisms of neurotoxicity. With current therapy, infection is never completely eradicated, and significant portions of toxicity seem mediated by indirect mechanisms that may continue even during antiretroviral therapy.