SummaryAlthough primary percutaneous coronary intervention (PCI) is the recommended method of reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI), fibrinolysis remains a beneficial alternative in patients who cannot be reperfused timely with primary PCI, and is still the preferred revascularisation strategy in many parts of the world where PCI facilities are unavailable. Because fibrinolysis is known to activate platelets and promote thrombin activity, concomitant administration of antiplatelet and anticoagulant therapies is needed to lower the risk for re-occlusion and to support mechanical interventions in patients undergoing rescue or delayed PCI. However, the addition of oral antiplatelet and parenteral anticoagulant drugs on top of fibrinolysis may come at the price of an increased risk of bleeding. The current availability of several antiplatelet and anticoagulant therapies often leads to questions about the optimal selection in STEMI patients treated with fibrinolytics. This article appraises current evidences for the management of adjunctive antiplatelet and anticoagulant therapies in patients with STEMI undergoing fibrinolysis followed by rescue or delayed PCI.