Stroke is the third most common cause of death, particularly of the elderly. Despite considerable advances in knowledge about the mechanisms of cell death after stroke, a treatment for stroke remains exclusive. For a long time, estrogen was thought of only as a " sex hormone". Studies have documented that estrogen plays an important role in regulating behavioral and physiological events beyond the reproductive system. Most animal studies have shown that estrogens exert neuroprotective and neurogenesis effects in vivo and in vitro after ischemic stroke. However, clinical and epidemiological evidence shows that estrogen increases the risk of coronary heart disease, stroke, and breast cancer. The discrepancy between animal studies and clinical data emphasizes the importance of performing further investigations using appropriate animal models, and gaining a deeper understanding of the mechanisms of estrogen-mediated neuroprotection and neurogenesis. This review focuses on recent advances in estrogen-mediated neuroprotection and neurogenesis after ischemic stroke, highlighting its potential molecular and cellular mechanisms.