Abstract Increasing evidence has profoundly challenged previously accepted concepts about the actions and clinical uses of nitroglycerin. Traditionally, use of this agent has been contraindicated in patients with acute myocardial infarction because of its hypotensive effects, and it has had no place in the therapeutic armamentarium of heart failure or arrhythmias. Recent investigations, however, suggest that nitroglycerin's usefulness may far transcend the role it has had for more than a century [1] in alleviating symptoms of angina pectoris. Nitroglycerin appears to be a potentially important addition to the treatment of both chronic heart failure and heart failure due to acute myocardial infarction. In addition, several reports have suggested that nitroglycerin decreases infarct size, has antiarrhythmic effects and reverses localized contraction abnormalities (asynergy) when due to ischemic dysfunction. This evidence is rapidly accumulating despite the fact that nitroglycerin's basic mechanisms of action have remained controversial.