The progression in unraveling the underlying biology of migraine has been achieved through the synthesis of experimental models in both animals and humans. Provocation studies, systematically conducted as double-blind crossover trials, along with imaging or biochemical markers, have been key in identifying vital molecular pathways, and steering the creation of targeted pharmacological treatments. Pharmacological models are favored for their consistency and repeatability, contributing to the reliability of the research. Recent human studies have shed light on the role of downstream potassium channels as a fundamental mechanism in migraine initiation. The integration of diverse approaches, encompassing state-of-the-art laboratory techniques, is positioned to deepen our understanding of the pathophysiological processes leading to migraine, opening the way for new, personalized treatments.