In seventeenth century, Thomas Willis pointed out the source of headache is distention of the vessels nearly identical with Wolf's twentieth century vascular hypothesis of migraine. The concept of the pathophysiology in migraine swung to neural cause by Edward Liveing (1873). The research evidence for special role of serotonin was revealed by modern approach and the mechanism of migraine was presented in trigeminovascular system. The development of the basic science leads to new treatments in headache clinic.