5-Hydroxytryptamine (5-HT, serotonin) is thought to play a part in the pathophysiology of migraine because platelet content of 5-HT in cubital and external jugular veins is reduced during migraine headache. Moreover migraine headache is precipitated by intramuscular injection of reserpine, which releases 5-HT from body stores, is relieved by the intravenous infusion of serotonin, and is prevented by the regular administration of medications that act on 5-HT receptors. Whether the peripheral action of 5-HT on cerebral and extracranial vessels or its central action as a neurotransmitter involved in bulbocortical and pain control pathways is of greater importance in the mechanism of migraine remains an open question. Increasing knowledge of the varieties of 5-HT receptor and the development of pharmacological agents that act specifically on certain receptors should give greater insight into the cause of migraine and increase the efficacy of treatment.