Experimental and clinical evidence is strongly in favor of a role for estrogens in migraine. It is clear that estrogen fluctuations represent trigger factors for the attacks, while the resolution of these fluctuations (menopause) may be associated to the remission or, conversely, to the worsening of the disease. However, the exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. The exact mechanisms and mediators underlying the effects of estrogens in migraine are largely unknown. In this review, we summarize clinical and preclinical data that are relevant for the role of estrogens in migraine and we discuss how estrogen modulation can be exploited positively to improve hormonal-related migraine.