The role of platelets as the link between ischemic heart disease and depression is reviewed. Platelet function abnormalities, including increased platelet reactivity, may predispose depressed patients to clotting diatheses and may explain their vulnerability to cardiovascular disease. Platelet physiologic characteristics, influences on platelet response, and indicators of platelet reactivity are discussed. Measurements of platelet activation, secretion, and aggregation have enabled the study of platelet responses in patients with major depression. The findings of clinical trials evaluating platelet responses to antidepressant treatment are described, and recommendations for future studies are proposed.