5-Hydroxytryptamine (5-HT; serotonin) has long been implicated in the aetiology of migraine but the evidence remains circumstantial and certainly not definitive. Numerous papers have reviewed the background which is briefly outlined here. Although the continued belief in the primary involvement of 5-HT in the genesis of a migraine attack has recently been questioned, many antimigraine drugs undeniably interact potently with 5-HT receptors. It can be argued, however, that their modest clinical benefit results from their pharmacological effects, be they mediated through 5-HT receptors or otherwise, independently of any pathophysiological involvement of endogenous 5-HT. Nevertheless, there seems convincing evidence that central release of 5-HT by various drug mechanisms causes migraine-like headache in migraineurs. It remains to be seen whether these drugs mimic the pathological event initiating the spontaneous migraine attack. Regardless of these considerations, the focus of research on 5-HT and migraine has proved to be enormously profitable over several decades, culminating recently in the identification of a novel, potentially important, antimigraine drug for the treatment of the acute attack. This drug, sumatriptan, is a selective cranial vasoconstrictor which mediates this effect by specifically activating a particular 5-HT1 receptor subtype. Undoubtedly a precise understanding of its clinical mechanism of action, which is currently being studied by a number of groups, will lead to a better understanding of the pathogenesis of migraine. Perhaps this in turn will help in finally determining whether migraine is a vascular disease and whether or not a disturbance of 5-HT is just epiphenomenal or is truly the primary initiating pathological event.