It has recently been shown that approximately 90% of cases of non-fatal myocardial infarction and many cases of sudden cardiac death are caused by disruption of a coronary atherosclerotic plaque, followed by occlusive thrombus formation. Secondly, the circadian pattern of myocardial infarction is well known to feature a prominent increase in the morning hours. Taken together, these factors may provide an opportunity to reduce deaths caused by cardiovascular disease. Findings indicate that, in many cases, plaque disruption and thrombus formation are triggered by the activities of the patient. It is postulated that onset occurs when a ‘vulnerable’ atherosclerotic plaque becomes disrupted and occlusive thrombus formation occurs. The occurrence of a myocardial infarction in the morning hours could result from the synchronization of a number of potential triggers. The importance of the recognition of the circadian variation of acute onset of myocardial infarction is that pharmacologic protection can be directed at the early waking hours. It would seem reasonable to propose that long-acting anti-ischemic agents would have an advantage over short-acting agents in providing protection against the morning occurrence of myocardial infarction. A future goal would be to design therapeutic regimens that would have the ability to sever the linkage between a potential triggering activity and the development of myocardial infarction.