Migraine is a common episodic headache that predominantly affects young adults, particularly women in their most productive years. Many of the prophylactic agents available today have side-effects that are not compatible with long-term use. The discovery that drugs influencing the renin-angiotensin system (RAS), which have few side-effects, were effective in some patients with migraine led to several studies investigating a possible link between the angiotensin system and migraine pathophysiology. Clinical trials indicated that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are effective in the prophylactic treatment of migraine. These findings are further supported by pharmacoepidemiological, genetic, and physiological studies. In addition, it is known that the RAS has neurophysiological, chemical, and immunological effects that are of relevance in migraine pathophysiology. On the basis of evidence presented in this review, we find it likely that the RAS has a clinically important role in migraine pathophysiology. The effect of ARBs and ACEIs on migraine is probably not attributable to their effect on blood pressure. The RAS has several actions that may be relevant in migraine pathophysiology, but the reason for the prophylactic effect of ARBs/ACEIs in migraine remains a matter of speculation.