Evidence from randomized clinical trials indicates that systemic administration of recombinant tissue plasminogen activator (rtPA) is a highly effective treatment for acute ischemic stroke, provided that treatment is administered within the first 3 h after stroke onset. An absolute increase in favorable outcome of up to 13% has been reported, and a pooled analysis of six randomized trials has shown that, although the sooner rtPA is given the greater the benefit, efficacy is present up to 4.5 h after stroke onset. Despite of the spreading use of tPA in different countries and continents, there are still a number of burdens and failures in the optimal accomplishment of thrombolytic treatment. rtPA is used in less than 4% of patients, reperfusion and complete recovery is achieved in less than 50% of patients, and treatment is denied to many patients. However, important advances in clinical investigation suggest that new aims and hopes will be achieved in the near future. Ultrasound-enhanced systemic thrombolysis, the use of MRI for selecting acute stroke patients for IV or IA thrombolysis after 3 h, mechanical embolus disruption or removal in proximal artery occlusions, and the potential usefulness of new biomarkers of blood brain barrier disruption and hemorrhagic risk are promising strategies that may improve the risk/benefit ratio and increase the number of patients who will benefit from thrombolytic therapy.

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