The key to treating acute ischemic stroke (AIS) is to start reperfusion therapy as early as possible to rescue the ischemic penumbra. Recombinant tissue plasminogen activator (rt-PA), which dissolves blood fibrous clots and recanalizes occluded vessels, has been approved as a preferred treatment for AIS in many countries and is included in treatment guidelines. With the publication of several relevant clinical research results, the application of thrombolytic therapy has been updated. This article reviews the research progress of hot issues such as green channel for stroke, broadened therapeutic window, new thrombolytic drugs, imaging screening, and cytoprotection for intravenous thrombolytic therapy of AIS, and hope to provide references for clinical decision-making.