Despite crucial advances in our knowledge of the pathologic mechanisms and the availability of effective diagnostic and treatment modalities, coronary atherothrombosis remains the most frequent cause of ischemic heart disease. Plaque disruption with superimposed thrombosis is the main cause of unstable angina, myocardial infarction, and sudden death. New findings have recently introduced exciting concepts that could have major impact on the treatment of the atherothrombotic disease. We will discuss the mechanisms that lead to the development of atherothrombosis and those responsible for the acute coronary syndromes, as well as some of the concepts derived from in vivo observations using new imaging technologies (eg, high-resolution magnetic resonance imaging).