Current thrombolytic therapy fails to induce early, complete, and sustained reperfusion in ±50% of the patients with ST-segment elevation acute coronary syndromes. There are two complementary approaches to improve thrombolytic therapy: the development of new fibrinolytics with enhanced fibrin specificity and/or reduced plasma clearance and the coadministration of new antithrombotic agents. The results obtained so far suggest that single-bolus fibrinolytic therapy is likely to replace the current infusions in the near future. This may result in a significantly earlier (prehospital) treatment of patients. The concomitant intravenous administration of a glycoprotein IIb/IIIa receptor antagonist (in combination with a reduced dose of a fibrinolytic) appears to be able to further enhance the efficacy for clot lysis without increasing the risk for bleeding complications. (Am Heart J 1999;138:S115-S120.)