Cardiovascular diseases (CVD) remain the leading causes of morbidity and mortality for men and women in developed societies. Aging is the primary risk factor for CVD in both sexes, as CVD prevalence increases with advancing age and >90% of CVD occurs in middle-aged and older men and women. However, sex hormone deficiency, particularly reductions in circulating levels of estrogen, as occurs during and after menopause, also plays an important role in age-associated increases in CVD risk in women. Aging increases CVD risk in part via direct effects on the heart and increases in systolic blood pressure, but much of the age-related elevation in risk is mediated by arterial dysfunction. Several types of arterial dysfunction contribute, but two of the most important changes are large elastic artery (aortic and carotid artery) stiffening and the development of endothelial dysfunction, as indicated by impaired nitric oxide (NO)-associated endothelium-dependent dilation. Although the exact mechanisms underlying age-related arterial dysfunction remain under investigation, it is clear that excessive superoxide-induced oxidative stress and chronic low-grade inflammation are the major processes involved. Regular aerobic exercise (AE) is one of the most effective strategies for reducing the risk of CVD with aging. Although AE lowers CVD risk in part by favorably modifying conventional risk factors such as blood pressure, fasting glucose and circulating lipids, much of benefits of AE are likely transduced through the maintenance of good arterial function and health1. Indeed, there is considerable evidence the AE inhibits large elastic artery stiffening and preserves vascular endothelial function with aging by maintaining NO bioavailability and suppressing vascular oxidative stress and inflammation1. For example, regular AE is associated with lower carotid-femoral pulse wave velocity (aortic stiffness) and enhanced carotid artery compliance with aging in both men and women1,2,3. Importantly, aortic stiffness and carotid compliance are improved in both middle-aged/older men and in postmenopausal women in response to an AE intervention1,2,3. There is some evidence to suggest that AE enhances carotid artery compliance in postmenopausal women by suppressing oxidative stress1. Regular AE has a strong vascular-protective effect on endothelial function with aging, at least in men1. Both macrovascular (e.g., brachial artery flow-mediated dilation, FMD) and microvascular (e.g., increases in forearm blood flow in response to brachial artery infusion of acetylcholine) endothelial function are preserved in late middle-aged/older men who regularly perform vigorous AE1,4,5. Consistent with such cross-sectional observations, AE training restores microvascular and macrovascular endothelial function to or close to levels observed in young healthy males4,5. These benefits are mediated by enhanced NO bioavailability and reduced vascular oxidative stress and inflammation1. Although some studies have reported AE-associated enhancement of vascular endothelial function in postmenopausal women, other studies, including our own, indicate a notable lack of effect in this group as a whole1. In a large cross-sectional comparison of healthy adults, we found that brachial artery FMD was ~50% greater in aerobically exercising vs. non-exercising middle-aged and older men, but did not differ in exercising vs. non-exercising (estrogen-deficient) postmenopausal women5. After an 8-week AE intervention, we observed a 50% improvement in brachial artery FMD in the men, but no change in the postmenopausal women5. A recent investigation by our laboratory confirmed these observations for macrovascular endothelial function, and extended our findings to show that microvascular endothelial function also does not differ between endurance exercise-trained and untrained healthy estrogen-deficient postmenopausal women6. To determine the role of estrogen deficiency in these observations, we studied the effects of AE training on endothelial function with and without prior chronic estrogen replacement7. We found that AE-induced improvements in brachial artery FMD only occurred in estrogen-replaced postmenopausal women, suggesting a critical permissive role of estrogen in transducing improvements in endothelial function with AE in this group. In summary, AE is associated with reduced arterial stiffness with aging in both men and women, and enhanced vascular endothelial function with aging in men. Further research is needed to understand the factors and physiological mechanisms, including those related to sex hormone bioavailability, underlying the inconsistent effects of AE on endothelial function in postmenopausal women.