Stroke is a major public health problem. The female population carries a higher stroke burden than the male population, both because females have a longer life expectancy and because most stroke deaths occur in women. Differences between the sexes in relation to stroke are increasingly being recognized; for example, among stroke survivors, women tend to have worse outcomes than men, as indicated by more-severe disability and an increased likelihood of institutionalization in women. Women and men with stroke also differ in their risk factor profiles, and they respond differently to primary-prevention and acute stroke treatment. Women experience variations in endogenous estrogens throughout their life cycle and might also be exposed to exogenous estrogens, both of which markedly affect the brain. An understanding of the effects of endogenous and exogenous estrogens on cerebral hemodynamics could guide research into explaining how hormone therapy increases the risk of stroke in postmenopausal women. This Review summarizes the sex differences related to stroke, and the effect of endogenous and exogenous hormones on the cerebrovasculature of the female brain. It also proposes potential research approaches, the results of which could fill in gaps in our knowledge regarding the mechanism of action of estrogen in the brain.