If excess influx of lipids predominates over the proliferative response, the atherosclerotic process progresses into the formation of vulnerable lesions. This type of lesions are the most clinically relevant since they are the pathogenic basis for plaque rupture and coronary thrombus formation. Plaque rupture is a mechanical event mainly determined by the fibrous cap thickness and the lipid core size. In addition, biological factors such as inflammatory infiltration may contribute to weakening and fracture of the fibrous cap. Exposure of plaque components to flowing blood following rupture is the key event to initiate thrombosis within coronary arteries. Local factors such as quantity (fissure size), quality (plaque composition) and rheology at the site of rupture, together with systemic factors inducing hypercoagulable or thombogenic states modulate thrombosis at the time of plaque rupture. The natural history of acute coronary syndromes probably mirrors that of the underlying plaque rupture and thrombus formation. Angina stabilization would correspond to resealing of a rupture, accentuation of symptoms to development of labile thrombosis, non-Q wave infarction to development of transient thrombotic occlusion, and Q-wave infarction to establishment of a persistent occlusive thrombosis. Furthermore, this natural history may be modified by vascular tone and presence of collateral circulation.