A growing interest in genetic research in migraine has resulted in the identification of several chromosomal regions that are involved in migraine. However, the identification of mutations in the genes for familial hemiplegic migraine (FHM) forms the only true molecular genetic knowledge of migraine thus far. The increased number of mutations in the FHM1 (CACNA1A) and the FHM2 (ATP1A2) genes allow studying the relationship between genetic findings in both genes and the clinical features in patients. A wide spectrum of symptoms is seen in patients. Additional cerebellar ataxia and (childhood) epilepsy can occur in FHM1 and FHM2. Functional studies show a dysfunction in ion transport as the key factor in the pathophysiology of (familial hemiplegic) migraine that predict an increased susceptibility to cortical spreading depression--the underlying mechanism of migraine aura.