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Introduction and Development: There appears to be a rationale for the use of thrombolysis in ischemic stroke. Streptokinase should no longer be used to treat acute ischemic stroke. However, thrombolytic treatment with recombinant tissue plasminogen activator (rt-PA) may have an important role in the management of acute stroke. The studies to-date highlight the importance of early intervention and careful patient selection. In the National Institute of Neurological Disorders and Stroke (NINDS) trial, treatment within three hours was associated with an improved functional outcome without an increase in mortality. In the European Cooperative Acute Stroke Study (ECASS), treatment of eligible patients resulted in improved neurologic and functional out come. In the Multicentre Acute Stroke Trial Europe (MAST-E) and Australian Streptokinase Trial (ASK) trials, later intervention was associated with an increased risk of cerebral hemorrhage and poor outcome., Conclusions: Successful use of thrombolytic therapy with rt-PA, therefore, depends on rapid assessment to exclude patients with hemorrhagic stroke or those at risk of hemorrhagic complications. It has been shown to be beneficial in patients treated within three hours who conform to the strict inclusion and exclusion criteria of the NINDS trial. Moreover, after the results of ECASS II, and the recent metaanalyses of all three major rt-PA trials, it seems that with strict selection criteria, expert CT-reading, adherence to the protocols and a stroke unit type approach, the time window for thrombolysis may be as long as six hours in selected patients.