The fact that traditional risk factors only account for approximately two thirds of cases of coronary artery disease (CAD) has stimulated increasing interest in the relationship between CAD and psychosocial factors. Five areas--chronic stress, socioeconomic status (SES), personality, depression, and social support--have been most thoroughly examined. There is evidence to support a causal relationship between chronic stress, SES, depression, and social support and development of CAD. In this article, we discuss the epidemiologic evidence linking psychosocial factors and CAD, and review the effects of psychosocial factors on several pathophysiologic mechanisms that have been proposed as potential mediators of CAD. The hypothalamic-pituitary-adrenal axis, hypertension and cardiovascular reactivity, endothelial function, inflammatory markers, platelets, coagulation factors, fibrinogen, lipids, glucose metabolism, and lifestyle factors have all been implicated in this process. Recently, the first intervention trials have been carried out, although with initially disappointing results. Reducing the cardiovascular risk due to these psychosocial factors will be one of the major health care challenges in the future.