Background.—Based largely on data from animal models, migraine is hypothesized to involve changes in neural function in brain areas that mediate nociception—specifically, the trigeminal nerve, spinal trigeminal nucleus, and thalamus. These hypotheses about migraine pathophysiology can be tested directly in humans for the first time, with recent advances in functional neuroimaging techniques, which allow assessment of functional activity of specific brain areas. This article discusses the hypothesized role of the trigeminovascular pain system in migraine, reviews recent findings involving functional imaging of the human trigeminal system, and considers applications of functional imaging in the study of migraine pathophysiology. Functional neuroimaging is the only noninvasive approach for the objective measurement of changes in neural activity in humans. Functional magnetic resonance imaging has been applied to the measurement of neural activation of the trigeminal nociceptive system in healthy volunteers, and in patients with pain syndromes such as trigeminal pain. Conclusions.—The demonstrated utility of functional magnetic resonance imaging at elucidating, in a regionally specific manner, the functional and temporal changes in neural activity in the trigeminal nociceptive system, promises to make it a useful tool for the study of migraine pathophysiology and the evaluation of therapeutic interventions.