Elevated cortisol in a subset of depressed patients is an enduring and well-replicated finding. Much interest has focused on the possible effects of depression on the hippocampus; however, an emerging body of evidence suggests an association between depression and non-central nervous system illnesses. In this review, data on the effects of depression on the brain and other organ systems sensitive to elevated cortisol are discussed. From searches of the MEDLINE, PSYCHINFO, and Current Contents databases, and other sources, articles were found specifically related to depression and physical changes or medical conditions associated with corticosteroid excess in patients with Cushing's disease, including cognitive impairment, hippocampal atrophy, increased waist-to-hip ratio, bone loss, hypertension, diabetes, peptic ulcers, and hyperlipidemia. Data are strongest for a relationship between elevated cortisol and depression, hippocampal atrophy, cognitive impairment, abdominal obesity, and loss of bone density. Some evidence suggests an association between depression and hypertension, peptic ulcers, and diabetes. Depression does not appear to be associated with hyperlipidemia. The data provide some support for similar health effects in depressed patients and patients with Cushing's disease or the metabolic syndrome; however, additional studies are needed relating systemic effects of depression to cortisol. Limitations of the current literature, treatment implications, and possible directions for future research are discussed.