The recognition that the onset of cardiovascular events follows a circadian periodicity and is frequently triggered by physical or mental stresses has created new possibilities for disease prevention. Morning peaks in occurrence are now well-documented for acute myocardial infarction, sudden cardiac death, transient myocardial ischemia, and ischemic stroke. The morning increase in events begins after subjects assume an upright posture and start the day's activities, during a time of sympathetic nervous system activation. Additional triggers of onset include heavy physical exertion, sexual activity, and anger, the risks of which have been quantified in the Determinants of Myocardial Infarction Onset Study. A general hypothesis of the triggering of coronary thrombosis has been proposed. The process begins with the development of a vulnerable atherosclerotic plaque, which may become disrupted by internal forces or by external hemodynamic or vasoconstrictive changes. Once disrupted, the plaque becomes a thrombogenic focus. An occlusive thrombus is more likely to form if other factors come into play to increase coagulability and vasoconstriction. From a clinical standpoint these findings provide theoretical support for the use of long-acting agents to provide adequate anti-ischemic protection during the higher risk morning hours in patients already taking anti-ischemic medications. From a research standpoint this new information on triggering provides clues to a mechanism of onset that might lead to more effective preventive therapy. Because most deaths from coronary artery disease occur before any type of acute therapy can be given, further efforts to explore this new field are warranted.