Most of the morbid events due to hypertension and other risk factors are related to alterations of the large arteries of the brain, the heart or the kidney. Historically large arteries have been considered as passive conduits of blood, and physicians, surgeons and pathologists were mainly interested on their anatomical lesions such as rupture, stenosis, aneurysm, or thrombosis. However we know that large arteries are not passive conduit tubes but are characterized by elastic properties and are able to synthesize many vasoactive substances. These properties make the arterial wall a major modulator of the blood pressure and more generally of the cardiovascular regulation. Aging, environmental and genetic factors are responsible for structural and functional changes of the arterial wall media (hypertrophy, extracellular matrix accumulation, calcium deposits) and of the vascular endothelium (decrease in the release of vasodilators and increased synthesis of vasoconstrictors), all that leading to a diminution of elasticity and increased stiffness. The alteration of large arteries elasticity has deleterious effects on the heart upstream being responsible for an inadequate increase in systolic pressure and a relative decrease in aortic diastolic pressure at any given value of mean arterial pressure. The elevation in systolic pressure causes a disproportionate increase in end-systolic stress, which is the principal hemodynamic factor which promotes the development of cardiac hypertrophy, increased ventricular oxygen consumption, and left ventricular hypertrophy and can compromise capacity for coronary perfusion. Clinical and epidemiological studies have raised the possibility that subjects with stiffer arteries have wide pulse pressure, and that stiffening of large arteries is associated with excess morbidity and mortality independently of mean blood pressure. In addition to its etiologic role in cardiovascular disease, increased arterial stiffness may serve as an early marker for the diagnosis of asymptomatic atherosclerotic lesions, or for the evaluation of the severity of these lesions. In this review we report data from clinical, epidemiological and genetic studies, suggesting that arterial stiffness may be considered as a significant marker and/or an independent cardiovascular risk factor. This new concept should lead physicians to evaluate arterial stiffness for the prognosis and treatment of cardiovascular patients.