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Introduction: Acute ischemic stroke is a leading cause of mortality and disability worldwide, particularly in low- and middle-income countries. Cerebral arterial occlusion leads to progressive tissue ischemia, so early recognition and timely treatment are crucial for prognosis. Significant advances in the management of ischemic stroke have been achieved in recent decades, particularly with the development of reperfusion therapies such as intravenous thrombolysis and mechanical thrombectomy. The expansion of therapeutic windows and the use of neuroimaging-based criteria enable a more personalized approach, emphasizing the importance of critically synthesizing recent evidence. Methodology: A systematic literature review was conducted in the PubMed and Virtual Health Library (VHL) databases, including studies published between 2020 and 2025. Descriptors related to ischemic stroke and reperfusion therapies were used, combined by Boolean operators. After applying filters and eligibility criteria and screening titles and abstracts, 16 studies were selected for full-text reading to comprise the final sample. The review included randomized clinical trials, meta-analyses, systematic reviews, and observational studies, in line with the PRISMA flowchart recommendations. Results and discussion: The 16 analyzed studies demonstrated the consistent benefits of reperfusion therapies in acute ischemic stroke, particularly when employed early and in combination. Intravenous thrombolysis is effective both as a standalone therapy and as a bridge therapy to mechanical thrombectomy, resulting in improved recanalization rates and functional outcomes. Reducing the time between interventions was a decisive factor in achieving better clinical results. Tenecteplase has emerged as a promising alternative to alteplase, as it is associated with higher rates of early and first-pass reperfusion without a significant increase in bleeding risk. Mechanical thrombectomy has shown functional benefit even in patients with large infarct cores, expanding the traditional eligibility criteria. Recent evidence has also indicated that adjuvant intra-arterial thrombolysis after endovascular reperfusion can optimize microvascular perfusion and improve functional independence in selected patients. Despite the advances, methodological heterogeneity was observed across the studies, limiting the generalizability of the results. Conclusion: The treatment of acute ischemic stroke has evolved into a multimodal, early, and individualized model. The integration of intravenous thrombolysis, mechanical thrombectomy, and adjuvant therapies has the potential to improve clinical outcomes and quality of life for patients significantly. However, further studies are needed to standardize protocols and refine selection criteria.