Early, complete, and sustained myocardial reperfusion is the principal goal of thrombolytic therapy. Unfortunately, the majority of patients treated today experience substantial delay before the initiation of thrombolytic therapy and, once treated, demonstrate suboptimal results of coronary thrombolysis. This is attributable, in part, to the underlying thrombus, which is platelet rich and resistant to plasminogen activators, and to the pro-thrombotic effects of fibrinolytics, which have no favourable effect on thrombin. Future therapeutic interventions will focus on improved reperfusion. Pharmacological strategies including novel plasminogen activators, direct thrombin inhibitors, and platelet glycoprotein IIb/IIIa inhibitors have all generated encouraging early clinical trial data and await further study. Mechanical reperfusion therapy with primary balloon angioplasty is particularly effective; its use is associated with the establishment of more complete infarct vessel patency than are thrombolytics. Considerable potential for the improvement of current reperfusion-directed therapy exists.