The clinical presentation and prognosis of coronary atherosclerosis depend more on plaque type than on plaque size. Stable plaques may narrow the arterial lumen and cause stable angina pectoris but are, otherwise, relatively harmless. In contrast, vulnerable plaques may rupture and thrombose, which is a potentially life-threatening event, being responsible for the development of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death. Gradual lipid accumulation and ongoing inflammation may destabilize a plaque, increasing the risk of sudden plaque disruption and thrombosis. External factors such as mechanical and hemodynamic stresses may be important in precipitating, or 'triggering', disruption of vulnerable plaques. It is, however, the ensuing thrombotic response that makes plaque disruption dangerous. The thrombotic response is dynamic with simultaneously ongoing thrombosis and thrombolysis, frequently causing intermittent flow obstruction leading to an unstable coronary syndrome. The challenge of today is to stabilize the vulnerable plaques, to prevent new formation of vulnerable plaques, and to prevent thrombosis on intact and disrupted plaques.