Major depression is a common psychiatric disorder associated with considerable suffering for individuals and their families. Indeed, the Medical Outcomes Study reported that the degree of physical and social impairment and the use of health care resources among patients with diagnosable depressive disorders is comparable only to that with chronic cardiac disease. In addition, recent studies in the United States and by the Cross-National Collaborative Group suggest that the cumulative lifetime incidence of major depression is increasing, with the more recent birth cohorts at increased risk. Unfortunately, major depression remains an underdiagnosed and undertreated condition. Evidence from the National Institute of Mental Health (NIMH) Collaborative Depression Study suggests that significant numbers of depressed patients receive little or no antidepressant therapy, despite the availability of effective treatments. Data from the NIMH Collaborative Depression Study further indicate that depression is a chronic and recurrent disorder. The diagnosis and treatment of depression in the elderly remain a significant challenge. Concomitant medical illness frequently obscures the diagnosis, and as a result, large numbers of depressed elderly go untreated. Although there is evidence that pharmacotherapy generally is as effective in the elderly as in younger adults, problems with side effects and compliance may limit the usefulness of some agents. Further investigation is needed to evaluate the effectiveness of antidepressant drugs in the very old and in those with concomitant medical illness.