This chapter discusses current and emerging strategies for migraine prevention and treatment in the light of the understanding of migraine pathophysiology. Discoveries in the field of migraine genetics, functional imaging, trigeminovascular pharmacology and physiology, and the biochemistry of events preceding and during migraine headache have become interwoven into a sophisticated integrated hypothesis that provides a framework for the understanding of antimigraine agents and the generation of new hypotheses to fuel the discovery of the next generation of acute and prophylactic antimigraine therapeutics. While the efficacy of current prophylactic medications has been established based on serendipity more than rational drug design, recent research has focused on the characterization of pathophysiological events leading to a migraine attack. This research has followed three main directions: (1) the study of biochemical and physiological processes leading to the development of neurogenic dural inflammation in animal models; (2) imaging studies of migraine patients during the aura phase of “classic” migraine; and (3) analysis of the genetic traits associated with different migraine subtypes. The chapter summarizes some of these findings and examines their clinical implications for emerging drug treatments.