Atherosclerosis is characterized by the response of the vessel wall to chronic multifactorial injury leading to the formation of atheromatous or fibrous plaques. Endothelial dysfunction represents an initial stage of atherosclerosis. In addition to endothelial dysfunction, smooth muscle dysfunction, metabolic abnormalities of the vessel wall including inflammation, oxidative stress and alterations of neurohormonal balance occur in various stages of atherosclerosis. We now propose a new clinical entity 'vascular failure', defined as the integration of all of these vascular abnormalities. Vascular failure is not an anatomical disease, but rather a comprehensive syndrome of abnormal vascular function. Vascular failure extends from risk factors to established atherosclerotic disease with arterial stenosis, and further to calcification of the vessel wall or serious vascular events that may be caused by plaque rupture and thromboembolic occlusion. We propose aggressive intervention to modify various risk factors, applying to this integrated new entity, vascular failure.