Animal studies have shown angiotensin converting enzyme (ACE) inhibitors to be effective agents for myocardial protection. They protect against lethal arrhythmias, preserve ventricular function, improve coronary reserve (especially after ischemia/reperfusion), and reverse myocardial hypertrophy. Human studies, on the other hand, have shown inconsistent results. The beneficial effects of ACE inhibitors demonstrated in animal studies provide major advantages for cardiac surgery. First, most cardiac surgery is performed under ischemic arrest induced by a cardioplegic solution, and the protective effects of ACE inhibition against reperfusion injury can reduce peri-operative mortality and morbidity. Second, most patients who undergo such surgery have myocardial hypertrophy due to hypertension, pressure or volume overload mediated by valve disease, or myocardial infarction. Ventricular hypertrophy is a strong risk factor for sudden death, probably from arrhythmia. Regression of the hypertrophy may prevent post-operative sudden death, thereby allowing for long-term benefits of surgery. In this paper, I review ACE inhibitor studies in animals and humans and the protective mechanisms involved. I also discuss why human studies show inconsistent results in spite of the fact that ACE inhibition is consistently protective in animal studies. Finally, I explore the potential clinical applications of ACE inhibitors in cardiac surgery.