The current status of thrombolytic therapy approved by the US Food and Drug Administration is intravenous recombinant plasminogen activator given within 3 h of the onset of ischemic stroke. Intra-arterial therapy is possible for up to 6 h but is not Food and Drug Administration-approved for this purpose. Based on current radiologic methods (i.e., magnetic resonance imaging and perfusion computed tomography scans), it is being increasingly realized that the time window for effective thrombolytic therapy is variable, and salvageable tissue in the form of the ischemic penumbra may exist for longer periods of time and could therefore offer a greater time window based on these imaging studies. Development of an effective neuroprotective drug would greatly enhance the stability of the penumbra and offer further opportunities for extending the time window for reperfusion.