Depression increases the risk of cardiac mortality and morbidity in patients with coronary heart disease (CHD), but the mechanisms that underlie this association remain unclear. This review considers the evidence for several behavioral and physiological mechanisms that might explain how depression increases the risk for incident coronary disease and for subsequent cardiac morbidity and mortality. The candidate mechanisms include: (1). antidepressant cardiotoxicity; (2). association of depression with cardiac risk factors such as cigarette smoking, hypertension, diabetes, and reduced functional capacity; (3). association of depression with greater coronary disease severity; (4). nonadherence to cardiac prevention and treatment regimens; (5). lower heart rate variability (HRV) reflecting altered cardiac autonomic tone; (6). increased platelet aggregation; and (7). inflammatory processes. Despite recent advances in our understanding of these potential mechanisms, further research is needed to determine how depression increases risk for cardiac morbidity and mortality.