Several recent studies have shown that 60–0% of coronary occlusions that cause acute coronary syndromes (such as unstable angina, myocardial infarction, or sudden ischemic death) evolve from atherosclerotic plaques that are only mildly to moderately obstructive. Numerous studies have demonstrated that coronary thrombosis, the immediate cause of acute coronary syndromes, is a consequence of plaque disruption. Most thrombotic events are related to deep plaque fissure, while superficial plaque erosion is the cause in a significant minority of cases. Thus, the mechanisms by which stable coronary artery disease (CAD) evolves into an unstable and potentially lethal acute coronary syndrome are related to plaque disruption and thrombosis. The vulnerability of a plaque to disruption appears to be determined by the presence of a large lipid-rich core, a thin fibrous cap, and an inflammatory cellular infiltrate, rather than by the size of the plaque or the severity of stenosis caused by a plaque before disruption. In addition to plaque disruption and thrombosis, enhanced vasoconstriction—a characteristic feature of CAD and dyslipidemia—may contribute to the clinical manifestations of CAD. Angiographic studies have demonstrated that risk factor modification produces a disproportionately greater reduction in ischemic clinical events than in anatomic regression of plaque, suggesting “plaque stabilization” may be the major mechanism of such clinical benefit. The relatively rapid attenuation of endothelial-mediated vasomotor dysfunction with the treatment of dyslipidemia lends credence to this concept.