Abstract: Migraine is a common and complex brain disorder. Studies found that 5-HT neurons arising from descending inhibition and/or facilitation systems involved in the pathophysiology and treatment of migraine by activating different 5-HT receptor subtypes located at trigeminal neurovascular pain pathways, which mediated the dual role, facilitating and/or inhibiting pain. In this review, we briefly describe the different 5-HT receptors associated with migraine, attempt to provide new insights into the clinical prevention and treatment of migraine.