Ischemic stroke is a devastating disorder with limited treatment options. Arterial recanalization with thrombolysis or mechanical thrombectomy may be used to restore perfusion in only a subset of cases. Collateral therapeutic strategies such as partial aortic occlusion attempt to reverse ischemia, the principal detrimental element in stroke pathophysiology. This article considers the theoretic basis of aortic occlusion as a therapeutic strategy for cerebral ischemia, procedural details employing the NeuroFlo (CoAxia, Maple Grove, MN) device, ongoing and prior clinical studies, and potential practice implications in the future. The hemodynamic mechanisms associated with flow redistribution due to aortic occlusion and impact on the dynamic role of collateral perfusion in the ischemic brain are considered. Targeting ischemia rather than clot disruption or consideration of venous hemodynamics and flow redistribution may initiate a radical transformation in stroke care. Ultimately, demonstration of a rational mechanism that averts ischemia will be essential.