Atherosclerotic plaque instability is directly involved in triggering acute coronary syndromes, including unstable angina, acute myocardial infarction, and sudden coronary death. Different and not completely unknown mechanisms are involved in the pathogenesis of the destabilisation of the vulnerable plaque; currently three mechanisms are considered to play a causal role in this process: embolization, vasoconstriction and plaque rupture that only in a few cases lead to thrombosis; in most cases it is repaired spontaneously. Therefore only some plaques lead to clinical manifestations whereas many others remain asymptomatic. It is possible formulate two hypothesis: in the first case there are different types of plaques, some with strong thrombogenic stimulus; in the second case all the plaques are considered to be equal and instead is the patient who in particular situations has an hypercoagulable state that leads to an high risk of acute coronary syndromes. The aim of this review is to analyze the complex mechanisms leading to plaque and patient vulnerability.