Migraine is a vascular headache but its pathophysiology is complex and multifactorial. Of the many pathophysiological factors that are implicated in migraine, changes in the metabolism of 5-hydroxytryptamine (5-HT) are the best documented. During the headache phase of migraine, urinary excretion of 5-hydroxyindoleacetic acid increases, whereas the blood 5-HT concentration decreases. Furthermore, in migraine patients reserpine precipitates a headache that can be alleviated by 5-HT. In the light of recent developments in the characterization and classification of the receptors for 5-HT, this article aims to discuss the relationship between the neural and cephalovascular 5-HT receptors and the antimigraine action of drugs.