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<h3>Purpose of the Review</h3> This article reviews recent breakthroughs in the treatment of acute ischemic stroke, mainly focusing on the evolution of endovascular thrombectomy, its impact on guidelines, and the need for and implications of next-generation randomized controlled trials. <h3>Recent Findings</h3> Endovascular thrombectomy is a powerful tool to treat large vessel occlusion strokes and multiple trials over the past 5 years have established its safety and efficacy in the treatment of anterior circulation large vessel occlusion strokes up to 24 hours from stroke onset. <h3>Summary</h3> In 2015, multiple landmark trials (MR CLEAN, ESCAPE, SWIFT PRIME, REVASCAT, and EXTEND IA) established the superiority of endovascular thrombectomy over medical management for the treatment of anterior circulation large vessel occlusion strokes. Endovascular thrombectomy has a strong treatment effect with a number needed to treat ranging from 3 to 10. These trials selected patients based on occlusion location (proximal anterior occlusion: internal carotid or middle cerebral artery), time from stroke onset (early window: up to 6–12 hours), and acceptable infarct burden (Alberta Stroke Program Early CT Score [ASPECTS] ≥6 or infarct volume <50 mL). In 2017, the DAWN and DEFUSE-3 trials successfully extended the time window up to 24 hours in appropriately selected patients. Societal and national thrombectomy guidelines have incorporated these findings and offer Class 1A recommendation to a subset of well-selected patients. Thrombectomy ineligible stroke subpopulations are being studied in ongoing randomized controlled trials. These trials, built on encouraging data from pooled analysis of early trials (HERMES collaboration) and emerging retrospective data, are studying large vessel occlusion strokes with mild deficits (National Institutes of Health Stroke Scale <6) and large infarct burden (core volume >70 mL).