The association of epilepsy and migraine has been long recognized. Migraine and epilepsy are both chronic disorders with episodic attacks. Furthermore, headache may be a premonitory or postdromic symptom of seizures, and migraine headaches may cause seizures per se (migralepsy). Migraine and epilepsy are comorbid, sharing pathophysiological mechanisms and common clinical features. Several recent studies identified common genetic and molecular substrates for migraine and epilepsy, including phenotypic-genotypic correlations with mutations in the CACNA1A, ATP1A2, and SCN1A genes, as well as in syndromes due to mutations in the SLC1A3, POLG, and C10orF2 genes. Herein, we review the relationship between migraine and epilepsy, focusing on clinical aspects and some recent pathophysiological and molecular studies.