Migraine is 3 times more common in postpubertal women than in men. Migraine is frequently exacerbated perimenstrually and commonly occurs exclusively at that time. It is often benefited by pregnancy and menopause. Estrogen withdrawal has been implicated as a mechanism for triggering migraines. The mechanism, however, is not well understood. Reproductive steroids have neuroactive properties that can modulate neuronal morphology and physiology. Increasing evidence suggests that circulating reproductive steroid levels regulate the balance of neuroexcitatory and neuroinhibitory activities in some brain regions by influencing synaptic plasticity. Estrogen has neuroexcitatory, whereas progesterone has neuroinhibitory, effects in most preclinical and clinical models. Several neurotransmitter systems that are implicated in migraine vary with reproductive steroid levels during the reproductive cycle. Estrogen stabilization may provide effective treatment in susceptible women, especially for catamenially exacerbated migraine.