The benefits of reperfusion in ST-elevation myocardial infarction are time-dependent no matter if epicardial blood flow is restored with primary percutaneous coronary intervention (PCI) or fibrinolysis. Rapid, sustained, and early restoration of flow in the infarct-related artery is necessary to minimize myocardial damage and to improve clinical outcomes. Though fibrinolytic therapy is widely available, it is limited by unpredictable efficacy, reinfarction, and intracranial hemorrhage. PCI has predictable success in opening the artery but is limited by delays in implementation, particularly in transfer patients. The selection of PCI or fibrinolytic therapy for ST-elevation myocardial infarction should be based on knowledge of the benefits and limitations of each strategy. While PCI is the superior strategy if employed rapidly by competent personnel, fibrinolytic therapy should be considered when significant delays to implementation of PCI are anticipated. Continued efforts, aimed at reducing the time to therapy with PCI and fibrinolysis, are of paramount importance.