<p>Migraine with aura is a phenotypically heterogeneous disorder characterized by scintillating scotoma, sensory, language, and/or motor disturbance often followed by a severe headache, and cutaneous allodynia. Cortical spreading depression (SD), a neuro-glial slowly propagating depolarizing wave, is the likely electrical event responsible for aura and a headache trigger. While clinical and preclinical observations support these relationships, there remains controversy over the role of SD as a model of migraine. This article as part of a series of debate articles will focus on data supporting SD as a model of migraine given the relationship of SD to migraine with aura, the evidence for SD as a trigger for trigeminal pain and SD and its downstream events as targets for migraine therapeutic intervention. Taken together, the bounty of evidence suggests SD has face, construct and predictive validity for migraine and can be used as a robust and reliable model of migraine with aura.</p>