The transition to the postmenopausal stage is associated with an increased risk for vascular diseases, including myocardial infarction and stroke. This has been linked to a decrease in estrogen production. Estrogens mediate their effects on the brain to a major extent through binding to nuclear receptors, estrogen receptor alpha and beta. It is possible that positive and adverse effects of estrogens are related to interactions between receptor genotypes and hormones. Notably, the estrogen receptor alpha polymorphism c 454-397T/T is associated with increased risk of hemorrhagic stroke, with a synergistic relationship between this genotype and hypertension. In experimental stroke settings estrogens influence recovery of cognitive functions, possibly via induction of neurotrophic factors and specific transcription factors including NGFI-A. This may be related to increased neuroplasticity in the hippocampal formation, a key area for memory processing. Individualized treatment with estrogen receptor medulators may be beneficial for individuals with an increased risk for stroke. Estrogens may also improve recovery after stroke.