Migraine headache is generated by the complex interaction of various players such as genetic predisposition, environmental triggers and intrinsic factors. The initial mechanism of a migraine attack has long been a controversial topic and exploring its origin is a challenging task. The scientific evidences so far indicate neuronal dysfunction in the cerebral cortex and particularly cortical spreading depression waves, as upstream to cascade of events leading to a migraine attack. Neocortex, evolutionary valuable part of the brain, is surrounded by pain sensing system that is finely tuned for detecting noxious signals. Abnormal functioning of more than one cortical area in migraineurs may suggest that hyperexcitable neocortex could be more easily challenged, overreacts and depolarize to repetitive sensorial stimuli and could switch to extreme excitability state where spreading depression waves occur. In this paper, I will review the data supporting the notion that migraine is a neuronal disorder where cortex has prime importance. Despite clear demonstration of cortical participation in migraine, the contribution of brain structures other than cortex to the development of migraine remains unclear.