The pathophysiology of migraine is incompletely understood. Neurobiological and gene regulation studies and advanced brain imaging are providing new insights into migraine pathogenesis. Recent discoveries have shed light on the neuronal events mediating both the aura and the headache phases of migraine, identifying a cerebral cortical origin of migraine aura, susceptibility to attacks based on cortical hyperexcitability, and the trigeminovascular system and its central projections as the origin of headache. This review focuses on abnormal modulation of brain nociceptive systems leading to central sensitization that may explain prolonged headache of the migraine attack and shift of the migraine phenotype from episodic to chronic headache.