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This review explores the epidemiological evidence for the relationship between depression and cardiovascular disease from a mechanistic standpoint. It is important to examine the biological, behavioral and social mechanisms to improve outcomes for depressed cardiac patients. A number of plausible biobehavioral mechanisms linking depression and cardiovascular disease have been identified. Tricyclic antidepressants have various effects on the cardiovascular system, while selective serotonin reuptake inhibitors are not associated with adverse cardiac effects and should, therefore, be the preferred choice for the treatment of most patients with comorbid depression and cardiovascular disease.