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Over the past three decades, the development of evidence-based medicine (EBM) has brought significant opportunities to the advancement of clinical practice in stroke medicine. Substantial EBM evidence has transformed clinical practice in multiple areas, including intravenous thrombolysis, thrombectomy, antiplatelet therapy, intracranial angioplasty, carotid endarterectomy and stenting, blood pressure lowering, blood glucose control, lipid-lowering and anti-inflammation (colchicine). Yet, the current body of evidence is not enough to meet the complex and evolving needs of stroke patients. This review was based on a special lecture, ‘What’s Next’ on the future of stroke medicine, delivered by Prof. Yongjun Wang in Beijing on 4 July 2025. The talk was attended by more than 10 recipients of the William M. Feinberg Award for Excellence in Clinical Stroke from around the world. This article reviews past achievements, highlights critical gaps in current knowledge and outlines future research priorities. By mapping out the trajectory of stroke medicine, this review aims to guide future efforts and illuminate the path forward for stroke medicine.