Physical stiffening of the large arteries is the central paradigm of vascular aging. Indeed, stiffening in the larger central arterial system, such as the aortic tree, significantly contributes to cardiovascular diseases in older individuals and is positively associated with systolic hypertension, coronary artery disease, stroke, heart failure and atrial fibrillation, which are the leading causes of mortality in the developed countries and also in the developing world as estimated in 2010 by World Health Organizations. Thus, better, less invasive and more accurate measures of arterial stiffness have been developed, which prove useful as diagnostic indices, pathophysiological markers and predictive indicators of disease. This article presents a review of the structural determinants of vascular stiffening, its pathophysiologic determinants and its implications for vascular research and medicine. A critical discussion of new techniques for assessing vascular stiffness is also presented.