Until a few years ago coronary atherosclerosis was thought to be a slowly progressive disease eventually leading to total coronary occlusion and myocardial infarction. Recent angiographic studies have shown, instead, that mild or moderate coronary stenoses have the highest risk of causing acute coronary syndromes when complicated by thrombus formation which, in turn, appears to be due to a complex interaction between the atherosclerotic background and acute ischemic stimuli. The tendency of the atherosclerotic background to develop thrombosis may be different in different patients, as indicated by the observation that the risk factor profile of patients who present with chronic coronary syndromes is different from that of patients who present with acute syndromes. The acute ischemic stimuli so far identified are: a sudden local thrombogenic stimulus; a transient systemic increase in systemic pro-coagulant activity; a transient increase in proximal and/or distal coronary tone. The recent observation of inflammatory cells activation, including T-lymphocytes, in patients with acute ischemic syndromes raises the intriguing possibility that a specific antigenic stimulus may play an important pathogenetic role.