Literature and folk wisdom have long linked depression and death; however, only recently have scientific studies examined the relation between them. Beginning in the 1970s, investigators compared mortality among patients treated for major depression and the general population. Nine of ten studies found an increased mortality from cardiovascular disease among depressed patients. However, such studies confound the relation between depression and its treatment. Community surveys circumvent this difficulty, but as these studies began to appear, other investigations revealed the strong association between depression and cigarette smoking, which made obvious a need to control for smoking. The first study to do this appeared in 1993, and not only did a relation between depression and mortality persist, but a relation between depression and the development of ischemic disease was revealed. In the past 2 years, six more community surveys have followed populations initially free of disease, and five have observed an increased risk of ischemic heart disease among depressed persons. Another research strategy is to start with subjects who have preexisting cardiovascular disease. Here, too, depression has consistently been associated with a worse outcome. In one well-designed study, patients with depression in the period immediately after a myocardial infarction were 3.5 times more likely to die than nondepressed patients. The basis of this association remains speculative. However, it is likely that the changes in the autonomic nervous system and platelets that are seen in depression account for a substantial portion of the association.