After participating in this activity, learners should be better able to:• Assess strategies for diagnosing depressive disorders in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS)• Identify factors that contribute to the development of depressive disorders in HIV/AIDS• Evaluate strategies for managing depressive disorders in HIV/AIDS ABSTRACT: Depressive disorders and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) are associated with major socioeconomic burdens. The negative impact of depressive disorders on HIV/AIDS is well known, including on treatment outcomes. Unfortunately, depressive disorders are underdiagnosed and undertreated in seropositive persons. This review summarizes clinically useful information on depressive disorders in HIV/AIDS. More specifically, we address assessment, differential diagnosis, contributing factors, management, and common challenges in the treatment of depressive disorders in seropositive individuals. Assessment and diagnosis of depression may be challenging in seropositive persons because of several biopsychosocial particularities associated with HIV/AIDS. One of the difficulties is the overlap between depression and HIV/AIDS symptoms, particularly in individuals with advanced AIDS, requiring consideration of a broad differential diagnosis. Several factors related to HIV/AIDS status contribute to the higher rates of depressive disorders, including infectious-immunological, psychosocial, and exogenous factors. The treatment of depressive disorders in HIV/AIDS involves three groups of interventions: (1) pharmacological interventions, (2) psychotherapeutic interventions, and (3) management of other contributing factors. Challenges in management include poor adherence to treatment and the risk of suicide. We provide evidence-based recommendations to improve assessment and management of depressive disorders in seropositive persons.