Improvements in the management of ST-segment elevation myocardial infarction(STEMI) have led to a reduction in the acute and long-term mortality rates. The first important decision in the care of patients who have STEMI is the method of reperfusion. Whether percutaneous intervention (PCI) or fibrinolytic therapy is chosen depends on a number of factors. This article reviews the data on PCI and fibrinolytics in the context of consensus guidelines, outlines adjunctive medical therapies important in the first 24 hours, and discusses a strategy for making the decisions and a hypothetical construct for evaluating new drugs and procedures in the future.