Sex dimorphisms are important factors that influence the outcomes after ischemic stroke, which include basic health status, cerebrovascular anatomy, hormone levels, and unique factors such as pregnancy and menopause. It is widely recognized that male and female respond differently to stroke. Women aged 45–74 years old showed a lower risk of stroke incidence compared to age-matched man. This kind of protection is lost with aging. Hence, there is increasing requirement to get a more comprehensive understanding of sex-based factors to stroke on stroke incidence, symptoms, and treatments. This review focuses on sex-specific mechanisms in response to stroke based on experimental studies and highlights recent findings in clinical studies including sex-differential evaluation and outcomes of stroke. Sex-based personalized medicine should be promising in stroke therapies.