Mental stress has long been implicated as a potential trigger of myocardial infarction and sudden cardiac death. This article reviews research conducted in the past two decades utilizing laboratory studies to investigate behaviorally-induced pathophysiological effects (including increased cardiac demand, decreased myocardial supply, and impaired dilation of coronary resistance vessels), in patients with coronary artery disease. The clinical significance of mental stress-induced ischemia is supported by findings of a predictive relationship of mental stress-induced ischemia for ambulatory ischemia and subsequent cardiac events. Mental stress-induced ventricular fibrillation, ventricular tachycardia, and T-wave alternans are also being explored as possible markers of arrhythmic vulnerability in human and animal models. T-wave alternans comparable to exercise can be induced by an anger-like state in an animal model, and with mental stress in patients with implantable cardioverter-defibrillators. Future directions for research on mental stress and cardiac events are suggested, including further studies of mechanisms of mental stress-induced arrhythmia and ischemia, additional studies of the prognostic significance of stress-induced ischemia and T-wave alternans, and use of pharmacological and psychosocial treatments for preventing stress-induced cardiac events.