Early intravenous thrombolysis within the first three hours has been considered in the United States as the first proven treatment in acute ischemic stroke. However, not all patients will respond to this therapy which is also associated with a risk of symptomatic, including fatal, intracranial hemorrhage. This overview addresses the issue of efficacy and safety of intravenous alteplase (tPA) in acute cerebral ischemia. The rationale for thrombolytic therapy and its limits are described. The controlled studies show that intravenous tPA is effective and safe when given under restrictive conditions within 3 hours after stroke onset, but the data for a larger therapeutic window between 3 and 6 hours remain controversial. The expected functional improvement and the risk of intracranial hemorrhage greatly depend on selective clinical and imaging criteria. For this purpose, MRI, using the diffusion- and perfusion-weighted sequences combined with MR- angiography, should be preferred to CT scan in the next future. Applicability of tPA thrombolysis in current neurological practice in Belgium is discussed. Before its generalization, this therapy should be restricted to specialized stroke centers and all treated patients should be recorded in a central data bank to guarantee continued surveillance.