This article provides a clinical nursing update on major neurological complications associated with HIV and AIDS. Life expectancy for those with AIDS has increased as a consequence of antiretroviral therapy, and thus, neurological complications remain a clinical challenge. Four significant diseases associated with HIV and AIDS are addressed: HIV-associated dementia, peripheral neuropathy, cryptococcal meningitis, and toxoplasmosis. Updated statistics, a review of pathophysiology, common manifestations, diagnostic tests, and standard treatments are discussed for each disease. Nursing considerations when caring for this population are reviewed and include assessment, safety, activities of daily living, pain management, and treatment adherence.