Objective: In this review we attempt to characterize the acute and chronic role of 5-HT2B receptors with regard to meningeal nociception in animal experiments and clinical data targeting migraine therapy. Background: Migraine is a common disabling neurovascular primary headache disease, the pathomechanism of which is still unclear. Serotonin (5-HT) and its receptors might play an important role in some aspects of migraine pathogenesis. The ability of the unselective 5-HT2B receptor agonist m-chlorophenylpiperazine to induce migraine attacks in migraine sufferers, the high affinity of prophylactic antimigraine drugs to this receptor and its expression in migraine-relevant structures like the dura mater argue for a role of 5-HT2B receptors in the pathogenesis of migraine attacks. Methods: For this review, the relevant databases such as PubMed, MEDLINE (R), Cochrane Library and EMBASE, respectively, were searched to December 2015 using the keywords "migraine, 5-HT2, trigeminal, neurogenic inflammation, nitric oxide, nitroxyl, vasodilatation, plasma protein extravasation" and combinations thereof. Conclusion: Our literature review suggests an important role of 5-HT2B receptor activation in meningeal nociception and the generation of migraine pain.