Cardiovascular disease is a leading cause of death in the western world with aging being one of the strongest predictors of cardiovascular events. Aging is associated with impaired vascular function due to endothelial dysfunction and altered redox balance, partly caused by an increased formation of reactive oxygen species combined with a reduction in the endogenous antioxidant capacity. The consequence of these alterations is a reduced bioavailability of nitric oxide (NO) with implications for aspects such as control of vascular tone and low grade inflammation. However, it is not only aging per se but also the accumulative influence of physical inactivity and other life-style factors, which negatively affect the vascular system. Regular physical activity improves NO bioavailability, the redox balance and the plasma lipid profile and, at a functional level, reduces or even reverses a majority of the observed detrimental effects of aging on vascular function. The effects of aging and physical activity on vascular function are, in part, related to alterations in cellular signaling through sirtuin-1, AMPK and the estrogen receptor. The polyphenol resveratrol can activate these same pathways and has, in animals and in vitro models, been shown to act as a partial mimetic of physical activity. However, support for beneficial effects of resveratrol in human is weak and studies even show that resveratrol supplementation, similarly to supplementation with other antioxidants, can counteract the positive effects of physical activity. Regular physical activity remains the most effective way of maintaining and improving vascular health status and caution should be taken regarding potential interference of supplements on training adaptations.