The remarkable decline in cardiovascular disease (CVD) experienced in developed countries over the last 40 years appears to have abated. Currently, many CVD patients continue to show cardiac events despite optimal treatment of traditional risk factors. This evidence suggests that additional interventions, particularly those aimed at nontraditional factors, might be useful for continuing the decline. Psychosocial stress is a newly recognized (nontraditional) risk factor that appears to contribute to all recognized mechanisms underlying cardiac events, specifically, (a) clustering of traditional cardiovascular risk factors, (b) endothelial dysfunction, (c) myocardial ischemia, (d) plaque rupture, (e) thrombosis, and (f) malignant arrhythmias. A better understanding of the behavioral and physiologic associations between psychosocial stress and CVD will assist researchers in identifying effective approaches for reducing or reversing the damaging effects of stress and may lead to further reductions of CVD morbidity and mortality.