The diagnosis coronary artery disease is classically based on patient's symptoms and morphology, as analyzed by angiography. The importance of risk factors for the development of coronary atherosclerosis and disturbance of coronary vasomotion is clearly established. However, microembolization of the coronary circulation has also to be taken into account. Microembolization may occur as a single or as multiple, repetitive events, and it may induce inflammatory responses. Spontaneous microembolization may occur, when the fibrous cap of an atheroma or fibroatheroma (Stary i.v. and Va) ruptures and the lipid pool with or without additional thrombus formation is washed out of the atheroma into the microcirculation. Such events with progressive thrombus formation are known as cyclic flow variations. Plaque rupture occurs more frequently than previously assumed, i.e. in 9% of patients without known heart disease suffering a traffic accident and in 22% of patients with hypertension and diabetes. Also, in patients dying from sudden death microembolization is frequently found. Patients with stable and unstable angina show not only signs of coronary plaque rupture and thrombus formation, but also microemboli and microinfarcts, the only difference between those with stable and unstable angina being the number of events. Appreciation of microembolization may help to better understand the pathogenesis of ischemic cardiomyopathy, diabetic cardiomyopathy and acute coronary syndromes, in particular in patients with normal coronary angiograms, but plaque rupture detected by intravascular ultrasound. Also, the benefit from glycoprotein IIb/IIIa receptor antagonist is better understood, when not only the prevention of thrombus formation in the epicardial atherosclerotic plaque, but also that of microemboli is taken into account. Microembolization also occurs during PTCA, inducing elevations of troponin T and I and elevations of the ST segment in the EKG. Elevated baseline coronary blood flow velocity, as a potential consequence of reactive hyperemia in myocardium surrounding areas of microembolization, is more frequent in patients with high frequency rotablation than in patients with stenting and in patients with PTCA. The hypothesis of iafrogenic microembolization during coronary interventions is now supported by the use of aspiration and filtration devices, where particles with a size of up to 700 microns have been retrieved. In the experiment, microembolization is characterized by perfusion-contraction mismatch, as the proportionate reduction of flow and function seen with an epicardial stenosis is lost and replaced by contractile dysfunction in the absence of reduced flow. The analysis of the coronary microcirculation, in addition to that of the morphology and function of epicardial coronary arteries, and in particular appreciation of the concept of microembolization will further improve the understanding of the pathophysiology and clinical symptoms of coronary artery disease.