Serious adverse cardiovascular events, including myocardial infarction, sudden cardiac death, and stroke, frequently result from thrombotic processes and rupture of atherosclerotic plaques. These events exhibit a pronounced circadian rhythmicity, with a marked peak in the morning hours when the patient assumes an upright posture and begins daily activities. However, it is not known if plaques rupture more frequently in the morning. This review will examine the epidemiologic evidence documenting this circadian phenomenon, consider its physiologic underpinnings, and discuss the implications of this pattern for rational pharmaceutical development. Finally, some practical implications regarding potential triggers of cardiovascular events will be discussed.