Coronary atherosclerosis without thrombosis is, in general, a benign disease. However, plaque disruption, or fissuring, with superimposed thrombosis, frequently complicates the course of coronary atherosclerosis. Small ruptures often remain clinically silent, whereas more extensive plaque rupture may cause the development of unstable angina, myocardial infarction, and sudden death. The risk of plaque disruption depends more on plaque type (composition) than on plaque size and stenosis severity. Major determinants of a plaque's vulnerability to rupture are: the size and consistency of the lipid-rich atheromatous core; the thickness of the fibrous cap covering the core; and ongoing inflammation and repair within the cap. Both plaque vulnerability (intrinsic disease) and rupture triggers (extrinsic forces) are important for plaque disruption. The former predisposes the plaque to rupture whereas the latter may precipitate it. The resultant thrombotic response, which is important for the clinical presentation and outcome, is portly determined by the reactivity of the circulating platelets and the balance between the fibrinolytic and coagulation systems. New ways of identification and treatment of the dangerous vulnerable plaques responsible for infarction and death, and optimization of antithrombotic treatment, are highly warranted in order to prevent and treat life-threatening coronary thrombosis.