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Stroke is a leading cause of death among women in the United States, and women are more affected by stroke than men. With women living longer than men, women experience not only a higher incidence of stroke but also more negative outcomes. Despite its lethal impact and high morbidity rate, the road from innovative bench research to improved clinical outcomes has been slow. This review explores the differential physiology, epidemiology, and clinical presentation of stroke between men and women, as well as the current status of laboratory and clinical data.