As our understanding of the multifactorial etiology of cardiovascular (CV) disorders evolves, the important role of behavioral and psychological factors in the development, prevention, and management of cardiac disease is increasingly appreciated. The link between mental stress and adverse cardiac events has been long recognized. A growing body of epidemiological observations has demonstrated that acute emotional stress may trigger angina, myocardial infarction (MI), or sudden death, whereas chronic exposure to stress contributes to the pathobiology of coronary artery disease (CAD). Experimental models have enabled quantification of the cardiac effects of psychological factors and allowed for detailed investigation of the underlying mechanisms. Of clinical relevance, interventions that reduce stress or improve stress management appear to be protective against CV events in addition to their efficacy in improving patient well-being and psychological parameters. Robust evidence supports the concept that acute mental stress may trigger an acute cardiac event or even sudden cardiac death. Epidemiological reports indicate that the incidence of acute coronary syndromes rises sharply in the setting of natural disasters such as hurricanes, earthquakes, and tsunamis. Similar to these infrequent, extreme scenarios, acute behavioral and emotional stressors encountered in everyday life (eg, anger or conflict) have also been implicated as potential triggers of myocardial ischemia and MI, malignant arrhythmia, and sudden cardiac death in patients with CAD. Consistent with the observations related to acute stress, chronic stressful conditions including occupation stressors, social relationships, and environmental stimuli have been linked to the development and progression of cardiac pathology, particularly CAD. The association between anxiety and CAD was initially demonstrated in patients with psychiatric disorders, but similar associations have also been found in general populations. Large-scale, community-based studies and prospective investigations have demonstrated a strong, dose-dependent association between anxiety disorders and cardiac death, particularly among men. The INTERHEART study demonstrated a 2-fold increase in the incidence of MI in relation to chronic stressors, even after adjusting for established risk factors such as age, gender, and smoking. The association between mental stress and CV risk appears to be comparable with, or even stronger than, the wellestablished risk conferred by hypercholesterolemia. In the Framingham study, relative risks were 1.3 for total cholesterol levels between 200 and 239 mg/dL and 1.9 for total cholesterol levels >240 mg/dL. Notably, risk gradients in relation to psychological stressors are comparable to the risk gradient of elevated cholesterol. Evidence exists that the association between mental stress and CV morbidity and mortality may in part be mediated by increased exposure to organic risk factors. Individuals exposed to psychological stressors are prone to unhealthy lifestyle behaviors including smoking, changes in dietary habits, increased intake of calories, decreased physical activity, manifestation of the so-called type-A personality, increased alcohol intake, higher coffee intake, and adverse changes in sleeping habits. These unfavorable behavioral responses may in part be responsible for the documented link between anxiety and CAD. Mental stress, however, also exerts direct effects on CV pathophysiology, characterized by marked sympathetic nervous system activation and release of catecholamines and corticosteroids. These neuroendocrine responses increase heart rate and blood pressure (BP), promote endothelial dysfunction, provoke vasoconstriction in atherosclerotic coronary arteries, and favor platelet activation and hypercoagulation. Together these pathobiological responses favor a proatherogenic and prothrombotic milieu that may contribute to the development and progression of atherosclerosis in the long-term and may increase myocardial oxygen demand and thus cause