Evidence obtained over the past decade indicates that myocardial infarction (MI) and sudden death are not random events but rather, in many cases, may be triggered by the daily activities of the subject. The importance of physical or mental stresses as triggers is suggested by the parallel morning increased onsets of MI, sudden cardiac death, and stroke. Unstable angina and MI are usually precipitated by thrombus formation over a disrupted plaque that causes partial or complete obstruction of coronary artery blood flow. This process may be caused by physiologic factors that lead to rupture of a vulnerable plaque and subsequent thrombosis. Beta-blockers and aspirin, which can diminish these physiologic processes, have been shown to blunt or abolish the morning peak of onset of acute MI. It is hypothesized that occlusive coronary thrombosis occurs when an atherosclerotic plaque becomes vulnerable to rupture, and mental or physical stress causes the plaque to rupture. Increases in coagulability or vasoconstriction triggered by daily activities may also contribute to complete occlusion of the coronary artery lumen. Recognition of the circadian variation of the onset of acute cardiovascular disease suggests the need for pharmacologic protection of patients during the vulnerable periods and provides clues to the mechanism of disease onset, the investigation of which may lead to improved methods of prevention.