Reperfusion therapy with pharmacologic fibrinolysis has provided striking reductions in mortality following acute ST-elevation myocardial infarction (STEMI). Nevertheless, the limitations of fibrinolysis are well recognized. Attempts to improve reperfusion with bolus-only fibrinolysis, and combination regimens including enoxaparin and glycoprotein IIb/IIIa inhibition have not led to improvements in mortality. Although both prehospital fibrinolysis and primary percutaneous coronary intervention (PCI) have reduced mortality, these strategies are associated with considerable logistic constraints, hampering widespread implementation. Potentially, a hybrid strategy combining the speed and simplicity of pharmacologic reperfusion with the ability to ensure epicardial vessel patency, and providing definitive management of the culprit lesion remains an attractive option. Facilitated PCI for STEMI may extend the benefit of myocardial reperfusion to a greater number of patients. The true benefit of this strategy will be defined by ongoing large-scale clinical trials. If results are positive, the clinical practice determinants required for the effective application of this strategy to the wider clinical community will need careful consideration.