Migraine is a ubiquitous neurologic disease that afflicts people of all ages. Its molecular pathogenesis involves peptides that promote intracranial vasodilation and modulate nociceptive transmission upon release from sensory afferents of cells in the trigeminal ganglion and parasympathetic efferents of cells in the sphenopalatine ganglion. Experimental data have confirmed that intravenous infusion of these vasoactive peptides induce migraine attacks in people with migraine, but it remains a point of scientific contention whether their site of action lies outside or within the central nervous system. In this context, it has been hypothesized that transient dysfunction of brain barriers before or during migraine attacks might facilitate the passage of migraine-inducing peptides into the central nervous system. Here, we review evidence suggestive of brain barrier dysfunction in migraine pathogenesis and conclude with lessons learned in order to provide directions for future research efforts.