[This Document is Protected by copyright and was first published by Frontiers. All rights reserved. it is reproduced with permission.] Aging is associated with structural and functional changes in the vasculature, including endothelial dysfunction, arterial stiffening and remodeling, impaired angiogenesis, and defective vascular repair, and with increased prevalence of atherosclerosis. Cardiovascular risk is similar for older men and women, but lower in women during their fertile years. Menopause is marked by the loss of endogenous estrogen production. Therefore, estrogens have been implicated in premenopausal protection from cardiovascular disease. Experimental and some clinical studies indicate that estrogen induces protective effects in vascular endothelium. Estradiol promotes endothelial vasodilator synthesis, including NO production through increased expression and activity of endothelial nitric oxide synthase, and modulates prostacyclin and thromboxane A2 release. The thromboxane A2 pathway is key to regulating vascular tone in females. Contrary to experimental results, some clinical trials have reported no cardiovascular benefit from estrogen replacement therapy in older postmenopausal women. These discrepancies could be due to the ¿Timing Hypothesis¿: estrogen-mediated vascular benefits occur only before the detrimental effects of aging are established in the vasculature. However, a gap remains in current knowledge of cardiovascular aging mechanisms in women. This review comprises clinical and experimental data on the effects of aging, estrogens, and hormonal replacement therapy on vascular function of females. We aim to clarify how menopause and aging contribute jointly to vascular aging and how estrogen modulates vascular response at different ages.