While thrombolytic therapy is approved in the United States and Canada for treatment of acute ischemic stroke, only a small number of patients are currently treated. Additional agents that could restore or improve cerebral flow are needed. Based on the experience in acute coronary syndromes, reperfusion agents such as platelet glycoprotein IIb/IIIa antagonists, alone or in combination with reduced doses of thrombolytic agents, have the potential for improving the safety and efficacy of recombinant tissue plasminogen activator (rt-PA). In addition, these newer agents may permit extension beyond the current 3-hour window from symptom onset used for systemic rt-PA.