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Wake-up stroke (WUS) refers to acute cerebrovascular disease without new onset stroke symptoms at bedtime whereas new onset neurological deficits after waking up or during sleep. With unknown onset time of symptoms, most cases are ischemic stroke. Recently, with the exploration of the pathogenesis of WUS and the application and development of imaging techniques such as electron computed tomography and magnetic resonance imaging, it is possible to explore the ischemic penumbra and cerebral perfusion, judge the presence of salvageable brain tissue, and develop a suitable treatment plan, which has become a hot spot in clinical research. This review focuses on the clinical diagnosis and treatment of stroke after waking up.