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Depression is highly prevalent in cardiac patients, with 20% to 40% of patients meeting criteria for major depressive disorder or experiencing an elevation in depressive symptoms. These depressive symptoms are often chronic and persistent, and they have been associated with the development and progression of coronary artery disease, worse health-related quality of life, poor physical functioning, recurrent cardiac events, and a 2- to 2.5-fold increased risk of mortality. Impaired adherence to health behaviors and adverse physiological effects of depression, including inflammation, endothelial dysfunction, platelet hyperactivity, and autonomic nervous system abnormalities, may link depression with adverse cardiac outcomes. Pharmacologic and psychotherapeutic interventions appear to be safe and effective at reducing depressive symptoms in patients with cardiovascular disease and may impact cardiac outcomes. Unfortunately, depression often is unrecognized and untreated in this population, despite the availability of brief screening tools that can be used for this purpose. We recommend the routine screening of cardiac patients for depression when there are adequate mechanisms for management and referral, such as available consulting psychiatrists or care management programs that facilitate the delivery of pharmacologic and psychotherapeutic treatments in this vulnerable population.