Although thrombolytic therapy for acute myocardial infarction (MI) is recommended without regard for infarct location, treatment results are less impressive for inferior than for anterior MI because the amount of myocardium at risk is smaller and less strategically located, and the mortality risk is lower. Whereas the risks associated with anterior MI are relatively constant, high risk subsets of patients with an inferior MI can be identified by simple electrocardiographic criteria, including left precordial ST segment depression, complete atrioventricular heart block and right precordial ST segment elevation. Unfortunately, none of the placebo-controlled, randomized trials have analyzed the benefit of thrombolytic therapy for inferior MI in high risk versus low risk subsets. Thrombolytic therapy should be more successful in reducing infarct size and decreasing mortality in high risk patients with an inferior MI. Thrombolytic therapy may not decrease hospital mortality in low risk patients (baseline risk 2% to 4%) or those with symptom duration > 6 h. Whereas it is arguable whether coronary angioplasty is superior to thrombolytic therapy in anterior MI, there are no mortality data to support using angioplasty as a primary or rescue reperfusion strategy instead of thrombolytic therapy in inferior MI, unless thrombolytic contraindications are present or the patient is in cardiogenic shock.