The measurement of vascular compliance has assumed increasing importance as a powerful predictor of cardiovascular and all-cause mortality. Arterial stiffness increases with the duration of diabetes, older age, and concomitant hypertension. Hyperglycemia may increase arterial stiffness in diabetes by reducing the bioactivity of endothelium-derived nitric oxide (NO) either by decreasing NO production or inactivating NO by interaction with oxygen-derived free radicals. New approaches to therapy, such as the use of advanced glycation end product "breakers," may potentially benefit patients with diabetes.