This article examines depression in 6 medical conditions: coronary artery disease (CAD), cancer, human immunodeficiency virus (HIV) infection, Parkinson's disease, pain, and the sex hormone changes of aging. Research is beginning to define specific biological and psychological mechanisms underlying the adverse interactions between depression and these medical conditions. Antidepressant medications, psychosocial therapies, and hormonal manipulations are effective in reducing depressive symptoms. Specific psychosocial interventions may increase longevity in CAD and cancer and may enhance quality of life in HIV infection. Newer antidepressants appear to be safer and better tolerated than older agents for medically ill patients, but do not appear to be as effective for neuropathic pain. Dopamine agonists may benefit depression associated with Parkinson's disease. Hormone replacement therapy may improve subsyndromal depressive symptoms in postmenopausal women and may enhance antidepressant response for older women with major depression.