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In common parlance, the close relationship between the heart and the mind is well known. Epidemiologic investigations of the last 20 years have put this relationship on an empirically confirmed basis: patients with heart disease, especially coronary artery disease, suffer from major depression at a rate exceeding chance alone. The reasons are still unknown, but current hypotheses focus on the influence of depression on endothelial function, blood coagulation, cardiac arrhythmias, inflammatory reactions, and lifestyle factors. Major depression worsens the prognosis of cardiologic disorders. Depression in patients with heart disease must be treated equally vigorously as in patients without heart disease. In patients with coronary artery disease and depression, only few controlled clinical studies are available, but have shown that selective serotonin reuptake inhibitors are effective and safe. They are therefore currently the drugs of choice. It is important for the clinician to consider major and minor depression in the differential diagnosis of psychiatric and somatic symptoms in patients with heart disease, to diagnose depression without delay, and promptly initiate an appropriate therapy according to current treatment guidelines.