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The approach to reperfusion therapies continues to evolve, and imaging is acquiring a greater role in the diagnostic work-up and treatment decisions as shown in recent clinical trials with extended time window. The 2018 American Heart Association/American Stroke Association guidelines reflect a paradigm shift in the management of AIS from "Time is Brain" to "Imaging is Brain." This review discusses the essential role of multimodal imaging developing from recent trials on therapy for AIS. © 2020 by the American Society of Neuroimaging.AIM