Spreading depolarization (SD) is a wave of mass neuronal and glial depolarization associated with net influx of cations and water. Prolonged SDs facilitate neuronal death. SD induces tone alterations in cerebral resistance arterioles, leading to either transient hyperperfusion (physiological neurovascular coupling) in healthy tissue or hypoperfusion (inverse neurovascular coupling = spreading ischemia) in tissue at risk for progressive damage. Spreading ischemia has been shown experimentally in an animal model replicating the conditions present following aneurysmal subarachnoid hemorrhage (aSAH), in animal models of the ischemic core and penumbra following middle cerebral artery occlusion, and in patients with aSAH. In animals, spreading ischemia produced widespread cortical necrosis. In patients, spreading ischemia occurred in temporal correlation with ischemic lesion development early and late after aSAH. We briefly review important features of SD and spreading ischemia following aSAH.