Ischemic stroke is a medical emergency and must be treated as quickly as possible according to the "time-is-brain" concept. At present, intravenous administration of recombinant tissue plasminogen activator (rt-PA) within the first 4.5 h from stroke onset is the only effective treatment but is currently still only approved within the first 3 h from onset of symptoms (0.9 mg/kg body weight, maximum dose 90 mg, 10% of the cumulative dose as bolus, remaining 90% subsequently infused within 60 min). The therapeutic effect of magnetic resonance imaging (MRI) based thrombolytic therapy beyond the 4.5 h time window remains to be proven. Proximal occlusions of the middle cerebral artery can be treated successfully within the first 6 h from stroke onset by catheter-based intra-arterial administration of plasminogen activator leading to a significant improvement of outcome. Acute basilar artery occlusion should be treated in specialized centres using intra-arterial application of urokinase, rt-PA or mechanical recanalization but intravenous thrombolysis beyond the 3 h window is an acceptable alternative.