Myocardial infarction is a dynamic evolutionary process which can progress over a relatively prolonged interval after its onset. The ultimate extent of damage depends on coronary artery anatomy, the balance between myocardial oxygen supply and demand, and metabolic modulators of myocardial injury. The possibility that methylprednisolone, a synthetic anti-inflammatory corticosteroid, may exert a beneficial effect on ischemic myocardium has been studied in both animal models and patients. However, the results of these experimental and clinical investigations have been controversial, in that some have demonstrated efficacy of the drug to limit extension of evolving myocardial infarction, while others have not. The effects of dose regimen and duration of methylprednisolone administration on preservation of myocardium and infarct size remain unclear, especially in clinical studies. The problem resides in the large interindividual variations among patients in degree and distribution of coronary disease, concomitant drugs, the accuracy of techniques for measuring and monitoring changes in myocardial infarct size, and the small numbers of patients involved in the majority of these studies. The absence of clarity will continue to cast doubts over the use of methylprednisolone until its marked beneficial effects can be significantly demonstrated.