As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion. A number of imaging modalities (vascular ultrasound, MRI, and coronary computed tomography) are used for non-invasive assessment of atherosclerosis; most of them can identify luminal stenosis, wall thickness and plaque volume and composition, and can even characterize the rupture-prone vulnerable plaques. Several classes of drugs, including statins, ACE inhibitors, -blockers, and antithrombotics, are able to reduce the plaque burden and the incidence of cardiovascular events; this may be attibutable, at least in part, to plaque-stabilizing effects and the improvement of endothelial dysfunction.