The unfortunate HIV-infected patient can expect that the virus will eventually destroy all ability to fight off opportunistic infection. Additionally, that the HIV can cause direct damage to the CNS is suspected, but probable. Common treatments of HIV-infected patients include medications with CNS and PNS side effects as well as metabolic disturbances that can result in altered mental status and/or seizures. The broad array of potential direct HIV effects, opportunistic infection, and malignancy-related central and peripheral manifestations, and drug actions and side effects are succinctly reviewed.