HIV infection in humans occurs primarily by mucosal infection during unprotected sexual activity or inoculation during intravenous drug use. HIV infection causes a progressive deterioration of protective cell-medicated immunity, specifically due the destruction of thymus-derived lymphocytes, called T-cell, during viral replication. Highly active antiretroviral therapy (HAART) reduces HIV viral replication and improves immune function against opportunistic infections, but it does not offer a cure for disease. Dental professionals should be able to recognize those with HIV infection by identifying the oral manifestations of fungal, viral, and bacterial infections or neoplasms that occur with immunodeficiency. Dental care providers should understand the adverse effects of HAART and communicate the importance of good oral health in managing disease.