Aging is one of the greatest risk factors in vascular diseases (VDs). During aging, there are structural and functional changes in the vasculature, including dilated lumen, altered intimal-medial thickness (IMT), vascular stiffness, endothelial dysfunction, increased endothelial apoptosis, matrix metalloproteinase (MMP) dysregulation, increased expression of inflammatory molecules, aggravated oxidative stress and shortened telomere length. These changes leave the body more susceptible to primary hypertension, stroke and coronary artery disease. Molecules that suppress these age-related changes would provide an excellent medical intervention for VDs. Mammalian Sir2 (SIRT1, a NAD+-dependent deacetylase), previously shown to extend the lifespan of lower organisms, is a promising target molecule to influence some aspects of vascular aging. In this review, we summarized roles of SIRT1 in various pathophysiological processes of vascular aging and proposed that SIRT1 and its activators can become novel therapeutic targets for age-related VDs.