Loss of normal autonomic nervous system control of heart rate and rhythm is an important risk factor for adverse cardiovascular events. After myocardial infarction, reduction in beat-to-beat heart rate variability, a measure of cardiac autonomic innervation by the brain, is a strong predictor of death. With loss of vagal innervation, as is noted in patients with severe neuropathy and in heart transplant recipients, there is loss of heart rate variability. It is speculated that decreased parasympathetic innervation exposes the heart to unopposed stimulation by sympathetic nerves. Individuals with high hostility scores and patients with anxiety or depressive disorders have low heart rate variability and may be at increased risk for cardiovascular death associated with coronary heart disease and arrhythmias. After myocardial infarction, depressed patients exhibit higher mortality rates compared with nondepressed patients. Men with “phobic anxiety,” a construct that appears to overlap substantially with panic disorder, also have higher rates of sudden cardiac death and coronary artery disease than control populations. The reduction in autonomic nervous system control to the heart may be one link between psychopathology and heart disease. Although tricyclic antidepressants reduce heart rate variability, at least one study has suggested that, in patients with panic disorder, treatment with the selective serotonin reuptake inhibitor paroxetine normalizes heart rate variability. Hence there is potential for the treatment of psychiatric disorders to affect positively the development and course of cardiovascular disease. (Am Heart J 2000;140:S77-83.)