Coronary artery disease remains a major cause of morbidity and mortality. Experimental and clinical data have indicated an important role of endothelin-1 at various subclinical and clinical stages of the disease. Endothelin-1 causes endothelial dysfunction and inflammation and may contribute to atherosclerotic plaque formation. During acute myocardial infarction, endothelin-1 enhances myocardial necrosis and arrhythmogenesis, but seems to exert a favorable effect on subsequent infarct healing and early ventricular remodeling. In the chronic postinfarction phase, endothelin-1 increases left ventricular afterload and participates in the myocardial fibrotic process. The progressive understanding of these actions has stimulated a large number of experimental and clinical studies examining the various effects of endothelin receptor blockade in coronary artery disease and chronic heart failure. However, this research has yielded largely contradictory results that have stirred scientific debates and controversies. This review summarizes the current state-of-the-art on this exciting topic, focusing on potential clinical ramifications.