It is widely accepted that diabetes mellitus (DM) impairs endothelial nitric oxide synthase activity as well as enhances the production of reactive oxygen species, thus resulting in diminished nitric oxide bioavailability and the consequent pro-atherogenetic alterations. Important biomarkers of the vasculature are related to endothelial dysfunction, to inflammatory and coagulation processes, and to oxidative stress in DM. Several therapeutic strategies might exert favorable effects on the vasculature of diabetic patients, such as insulin analogues, antihypertensive agents, statins, and hypoglycemic agents, whereas in spite of the prominent role of oxidative stress in diabetes, antioxidant therapy remains controversial. The use of specific biomarkers related to vascular function could be a useful therapeutic approach in such patients.