Acute ST-segment elevation myocardial infarction is estimated to occur in more than 500,000 people in the US every year. With the introduction of reperfusion therapy by fibrinolysis or primary angioplasty, mortality has significantly fallen. Although fibrinolysis is more readily available than primary angioplasty, the latter is more effective and results in better short-term and long-term outcomes if performed in a timely manner by an experienced operator and hospital team. The ischemic time, door-to-balloon time and clinical risk are important determinants of favorable outcome. Primary angioplasty is the preferred reperfusion strategy when symptom onset is longer than 3 h, in high-risk patients, such as those with cardiogenic shock, congestive heart failure or elderly age, and those with contraindications for fibrinolysis. Primary angioplasty is the preferred strategy in interventional facilities, with a goal door-to-balloon time of less than 90 min. For patients who present to noninterventional facilities, transfer to a hospital capable of primary angioplasty is safe and effective if the additional treatment delay is less than 90 min. Facilitated percutaneous coronary intervention has been shown in several small trials to offer early vessel patency and improve outcomes compared with fibrinolysis alone, but has not been shown to reduce mortality. Larger trials are ongoing to evaluate the benefit of this approach. The establishment of an effective and efficient system for the rapid transport of patients to centers capable and experienced in primary angioplasty is severely needed to provide optimum treatment and outcomes to patients with ST-segment elevation acute myocardial infarction.