The striking clinical benefits that can be derived from thrombolytic therapy in acute myocardial infarction emphasize the need for further improvement of our reperfusion strategies. New approaches in that direction include the development of more efficient thrombolytic drugs as well as an adjunctive therapy to control the ongoing thrombogenic stimulation. Aspirin is already useful in this regard as well as heparin with recombinant tissue-type plasminogen activator. The field of antithrombotic therapy is rapidly expanding with the development of patent drugs targeted at inhibiting specific steps of platelet activation and of the coagulation cascade. This new therapy provides opportunities to better understand the pathophysiological processes involved in acute ischemic syndromes and to modulate them. This article reviews the adjunctive antithrombotic therapy currently available or under clinical investigation with the potential of enhancing the benefits of thrombolysis.