A common problem facing the psychiatric consultant and the medical practitioner is evaluating depression in patients with concurrent medical illnesses. Depression is difficult to recognize in the medically ill, often presenting with "masked" symptoms and organized into unique syndromes. A primary concern of the clinician is identifying those patients who are likely to benefit from an antidepressant trial. Although antidepressants have been shown to sometimes be of benefit in medical populations, the symptoms predicting antidepressant response remain poorly defined. Important directions for future research include 1) evaluating the safety and efficacy of newer antidepressants in the medically ill and 2) identifying those depressive syndromes that may be responsive to pharmacotherapy.