Neurological disorders, notably a dementia, are central to the outcome and medical management of patients with AIDS. These disorders are the consequence of both a secondary immunosuppression and a distinct, primary pathological process due directly to the virus. This pathological process involves a range of inflammatory disorders in association with synaptic, dendritic and neuronal degeneration. Recent evidence indicates that the degeneration is a consequence of HIV derived factors and of alterations in the expression of host factors. Furthermore, the degeneration may have a final common pathway, involving alterations in calcium homeostasis and ending with neuronal loss through apoptosis. In this review we will concentrate on the primary damage due to the HIV virus and describe its relationship to the development of clinical dementia. The timing of this damage and the mechanisms by which it occurs will be outlined.