Rapid reperfusion is the key treatment goal in patients with ST-segment elevation myocardial infarction (STEMI). The American College of Cardiology-American Heart Association (ACC-AHA) 2004 guidelines for the management of STEMI include recommendations for pharmacologic reperfusion with use of fibrinolytic agents. Fibrinolytic agents are the preferred pharmacologic class for the management of STEMI because of their ability to achieve reperfusion and to restore blood flow when administered within 12 hours of symptom onset. Four fibrinolytic agents are approved for the treatment of STEMI in the United States-streptokinase, alteplase, reteplase, and tenecteplase. Several clinical trials have demonstrated the beneficial effects of these therapies in reducing mortality rates in patients with suspected acute myocardial infarction. Alteplase is administered as an intravenous infusion. However, the relatively long half-lives of reteplase and tenecteplase enable bolus administration, which may be more convenient and less time consuming. Reteplase is administered as a double bolus, and dosing does not depend on the patient's weight; tenecteplase is administered as a single bolus, and dosing is weight based. Adherence to the ACC-AHA guidelines, as well as knowledge about the available fibrinolytic agents, is essential for physicians and pharmacists to make informed decisions regarding appropriate pharmacologic reperfusion strategies.