By the end of their reproductive life cycle, roughly 40% of women have experienced migraine. Women have certain times of vulnerability for migraine that relate to abrupt declines in estrogen levels. Specifically, the prevalence of migraine is higher after menarche, during menstruation, during the postpartum period, and during perimenopause, but it is commonly lower during the second and third trimesters of pregnancy and the postmenopausal years. Therapeutic strategies for migraine management include hormonal manipulation aimed at eliminating or minimizing the decreases in estrogen that trigger the especially severe menstrual-related attacks. This article reviews special considerations for triptan use in pregnant and lactating women and in women with high risk for cardiovascular disease. Health care professionals caring for women throughout their life span should be aware of these important sex-based differences in migraine and migraine management.