Ovarian hormones have a significant effect on the central nervous system of female migraineurs. Reproductive milestones such as menarche, pregnancy, and menopause are associated with changes in the clinical course of migraine headache. Migraine attacks are commonly triggered during declines in serum estrogen levels that occur before and during the time of menstruation. Therefore, substantial clinical evidence suggests that changes in ovarian hormones affect migraine headache. This represents the first of two manuscripts defining the role of ovarian hormones in the pathogenesis of migraine headache. The purpose of the first article will be to review the molecular and neurophysiologic effects of estrogen and progesterone on neurotransmitter systems and pain processing networks relevant to migraine headache. The second manuscript will focus on the clinical studies detailing the influence of estrogen and progesterone on migraine headache.