Several key advances in understanding of pathophysiology now provide the opportunity to develop improved treatment and prevention strategies. First, the importance o mechanism of plaque rupture and thrombosis in onset of myocardial infarction. Second, there has been demonstrated, that plaques that lead to acute occlusion often have only a mild degree of stenosis. A third advance that has stimulated the field has been the recognition that time of onset of cardiac events is not random but instead shows a circadian pattern of onset. In the decade since the 1985 observation by Muller a spol. that the frequency of onset of myocardial infarction peaks at 9 a.m., numerous publications have supported this observation not only for myocardial infarction, but also for sudden cardiac death, transient myocardial ischemia, and stroke. Refinement of these epidemiological observations has led, first, to the conclusion that the morning peak in disease onset is due in part to the physical and mental stressors associated with morning awakening and activity and, second, that stressors such as heavy physical activity and anger can trigger acute cardiovascular events.