Females develop less age-dependent loss of renal function, which may be in part due to cardiorenal protective effects of estrogens. The impact of androgen level on cardiovascular-renal health is controversial. Estrogen acts through multiple mechanisms, sometimes beneficial, sometimes damaging, which makes it difficult to predict the effect of hormone replacement therapy (HRT) in an aging population. Nitric oxide (NO) deficiency occurs in aging and contributes to age-dependent cardiovascular risk and kidney damage. The increased oxidative stress of aging has effects at multiple sites in the NO biosynthetic pathway to lower NO production/action. Loss of NO together with activated angiotensin promotes some of the decrements in cardiovascular-renal function seen with age, which may be related to actions of the sex steroids.