Once considered part of the normal aging process, the development of isolated systolic hypertension represents a late manifestation of increased arterial stiffness in older people. Furthermore, isolated systolic hypertension is the single most frequent subtype of hypertension in the US adult population. Indeed, central arterial stiffness rather than peripheral vascular resistance becomes the dominant hemodynamic factor in both normotensive and hypertensive individuals after the age of 50-60 years. Stiffening disease, an age-related degeneration of the elastic elements of the thoracic aorta, is associated with a widening of brachial pulse pressure. Brachial pulse pressure predicts future cardiovascular disease events. However, pressure wave amplification produces higher brachial than aortic pressures and, therefore, central rather than peripheral blood pressure indices are more reliable measures of cardiovascular risk. Stiffening disease of aging is accompanied by early wave reflection, which results in a significant augmentation of central systolic pressure in late systole and further adds to increased cardiac afterload--so-called ventricular-vascular uncoupling. Diabetes, impaired renal function, and untreated or poorly treated hypertension may lead to premature arterial stiffening; its consequences are stiffening and hypertrophy of the left ventricle and predisposition to coronary heart disease, heart failure, stroke, vascular dementia, and chronic kidney disease.