3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are greatly contributed to the treatment of hypercholesterolemia, and constitute an important part of comprehensive strategies for the treatment of cardiovascular disease in the 21st century. Particularly, a strategy for preventing acute coronary syndrome (ACS), the most important complication of hyperlipidemia, is urgently needed. Recent research has revealed a new mechanism of prevention of coronary heart disease by statins: they not only lowered cholesterol level as previously reported, but also contribute directly to plaque stabilization. Among many statins recently marketed, some act directly onto the blood vessel wall to stabilize plaques already formed (so-called vascular statins), while statins are originally classified as chemical or non-chemical. At the same time, reports on pleiotropic activities of statins, including improvement of osteoporosis, have accumulated to suggest an extended role of statins, not merely as a hypolipidemic agent but also possibly an antiarteriosclerotic/ anti-aging drug. This article reviews the direct action of statins on the blood vessel wall, with reference to classification of statins based on difference in action on the blood vessel wall (hepatic statins vs. vascular statins).