Depression is a prevalent and interfering, yet potentially treatable illness commonly comorbid with HIV/AIDS. In HIV, symptoms and diagnoses of depression have been associated with poor adherence to antiretroviral medication regimens and to accelerated disease progression. This article is a review of the existing literature on the treatment of depression in the context of HIV, including: (1) psychosocial and behavioral health interventions that directly target Diagnostic and Statistical Manual of Mental Disorders (DSM) unipolar depressive disorders, (2) psychosocial interventions that indirectly target depressive symptoms, and (3) psychopharmacologic treatment studies for DSM-IV unipolar depressive disorders. Psychosocial and psychopharmacologic treatments of depression appear to be effective for individuals with HIV. However, additional methodologically rigorous trials are needed for definitive inferences regarding treatment efficacy. Because of the high frequency of depression comorbid with HIV, and the association of depression with important self-care behaviors in this population, identification of efficacious treatments for depression has the potential to improve both overall quality of life and, potentially, health outcomes.