Leptin is an adipocytokine that consists of 167 amino acids. It functions as a regulator of hunger and energy expenditure. Leptin loses its ability to carry out its physiological function at high serum levels, and many studies have associated this loss of function with the development of coronary artery disease (CAD). This literature review aims to outline the steps by which leptin leads to CAD and atherosclerosis. Two independent researchers extracted animal and human studies from PubMed and Google Scholar databases. We applied PubMed search builder options: pathology, pathophysiology, metabolism, and physiology to focus the search results. This study concluded that the mechanism by which leptin might lead to CAD via pressor and depressor effects on vascular tone, enhancing atherosclerotic plaques, and through numerous single nucleotide polymorphisms, the most common being that of the leptin receptor gene rs113701.