During the first 1 to 2 h of the classical migraine attack a hypoperfusion develops which starts in the posterior part of the brain and progresses anteriorly at a rate of 2-3mm/min. The hypoperfusion stops at primary sulci outlining major cortical macro-and microstructural changes, but seems not to be inhibited by other changes of the cortical architecture. The low flow regions are cortical and the low flow persists for 4–6 h, until the attack abates. Regions of hyperperfusion are either minor or non-existent. A similar behavior characterizes the velocity and mode of evolution of a cortical spreading depression, a transient perturbation of cortical neuronal function which has profound and long-lasting influence on the cortical blood flow. This paper briefly summarizes the arguments which have been put forward in recent years suggesting that spreading depression is a pathogenetic mechanism of migraine.