Migraine and epilepsy share several clinical features, and epilepsy is a comorbid condition of migraine. Clinical studies have shown that some antiepileptic drugs are effective at preventing migraine attacks. A rationale for their use in migraine prophylaxis is the hypothesis that migraine and epilepsy share several common pathogenetic mechanisms. An imbalance between excitatory glutamate-mediated transmission and GABA-mediated inhibition in specific brain areas has been postulated in these two pathological conditions. Moreover, abnormal activation of voltage-operated ionic channels has been implicated in both migraine and epilepsy. Cortical spreading depression has been found to be involved in the pathophysiology of epilepsy, in addition to the generation of migraine aura.