In the last decennium, thrombolytic therapy has changed the management of acute ischemic stroke. Randomized clinical studies have demonstrated that intravenous thrombolysis with tissue plasminogen activator improves functional outcomes. Recently the time window for intravenous thrombolysis has been extended from 3 to 4.5 hours after stroke onset, which will allow more stroke patients to benefit from this treatment. Currently several studies are investigating how to improve recanalization rates of thrombolytic therapy. In this review several aspects of intravenous and intra-arterial thrombolysis are discussed.