In patients with ischemic heart disease, contractility of dysfunctional myocardium may improve through metabolic modulation. Trimetazidine is the first of a new class of cytoprotective agents with antianginal properties. There is recent evidence that trimetazidine reduces fatty acid beta-oxidation and stimulates glucose oxidation by selective inhibition of 3-ketoacyl coenzyme A thiolase. In experimentally-induced myocardial ischemia, trimetazidine increases glucose oxidation by 210%, and this effect is associated with a 37% increase of pyruvate dehydrogenase. The increased rate of glucose oxidation reduces hydrogen ions and lactate accumulation, translating into improved myocardial contractility. In a recent randomized longitudinal placebo-controlled study in humans with ischemic cardiomyopathy, trimetazidine improved the contractile response of dysfunctional myocardium at doses of 20 mg tid for 8 weeks. This effect was associated with enhanced functional capacity and a higher ischemic threshold. The lack of effects on heart rate and blood pressure offers potential advantage in conditions of bradycardia and arterial hypotension. These important benefits need to be confirmed in larger longitudinal trials.