This special issue of Molecular and Cellular Biochemistry contains original research papers as well as invited reviews focused in the field of cardiac metabolism and its regulation under normal and disease conditions. These papers cover many areas under intensive and rapid development such as the regulation of fatty acid oxidation in the heart, the role of cardiac glycogen during ischemia, the role of CPT I isoenzymes, the pathophysiology of diabetic cardiomyopathy, cardiac protection through regulation of energy production, the role of fatty acid binding protein under normal and pathological conditions, and several other important topics in this area of research. We hope that this special issue of Molecular and Cellular Biochemistry provides an up-to-date source of information for scientists and clinicians interested in the mechanism by which cardiac metabolism is regulated in health and disease and the mechanistic relationship between disturbances in cardiac metabolism and the genesis of cardiovascular diseases.