<p>Trimetazidine is a metabolic modulator that acts as a competitive inhibitor of the terminal enzyme in the β-oxidation pathway to shift energy substrate from free fatty acids to the more oxygen-efficient glucose metabolism. The resulting conservation of cellular adenosine triphosphate generation in the face of ischemia/hypoxia mediates the anti-ischemic efficacy of trimetazidine. Clinically, trimetazidine has been approved as an add-on treatment in patients with symptomatic angina that is poorly controlled with first-line agents or who cannot tolerate the first-line therapy. In addition, trimetazidine has demonstrated antioxidant, cytoprotective, and anti-apoptotic activity with applications beyond angina. The aim of this review was to summarize the mechanism of action and anti-anginal efficacy of trimetazidine and to discuss the putative role of these pleiotropic effects and the evidence behind its application in cardiovascular diseases in general.</p>