The two most common forms of migraine are migraine with and without aura and are thought to be genetically complex. In contrast, familial hemiplegic migraine is inherited in an autosomal dominant fashion. Disease causing mutations and genes responsible for the phenotpyes of familial hemiplegic migraine were studied in common forms of migraine using linkage analysis, mutation analysis and association studies. Respective loci or known mutations in these genes were not present in large samples of migraine families or case series. Headache is a prominent feature in mitochondrial encephalomyopathies; neither the 3234A->G nor 8344A->G mutation was found in large sample of migraineurs. By Screening the entire x-chromosome for linkage in 61 families we identified a new locus for migraine on Xp22. In a pathophysiological study, a discreet disturbance in smooth pursuit eye movements was documented, linking clinical presentation and possible anatomic origin (brainstem). Chronicity was investigated by analysing pain coping strategies in migraineurs and at a molecular level by studying a possible influence of the serotonergic system on chronicity and depression.