Hypertension is a major risk factor for cardiovascular disease and renal disease. After menopause, the incidence of hypertension increases in women to levels that equal or exceed that in men, suggesting a protective role of female sex hormones. Salt sensitivity of blood pressure is associated with an increased risk for development of hypertension and cardiovascular disease. We and others have demonstrated that after menopause, the prevalence of salt sensitivity increases, suggesting that female sex hormones influence renal sodium handling and blood pressure regulation. A homeostatic balance between the counteracting effects of nitric oxide (NO) and angiotensin (Ang) II on pressure natriuresis, renal hemodynamics, tubular sodium reabsorption, and oxidative stress plays an important role in modulating salt sensitivity as well as hypertensive end-organ injury. Estrogens modulate the activity and expression of NO and Ang II. We infer that after menopause, estrogen deficiency promotes an unbalance between NO and Ang II, resulting in disturbed renal sodium handling, oxidative stress, and hypertension, particularly in genetically prone women. A better understanding of the mechanisms underlying the development of postmenopausal hypertension and associated cardiovascular and renal diseases should provide insights into preventive and therapeutic strategies.