The current minireview aims to assess the implications of epicardial fat secretory function in the development of coronary artery disease. The epicardial adipose tissue (EAT) is a visceral fat depot that has been described as a cardiovascular risk factor. In addition to its mechanical protection role and physiological secretory function, it seems that various secretion products of the epicardial fat are responsible for metabolic disturbances at the level of the cardiac muscle when in association with pre-existing pathological conditions, such as metabolic syndrome. There is a pathological reduction in sarcomere shortening, abnormal cytosolic Ca²⁺ fluxes, reduced expression of sarcoplasmic endoplasmic reticulum ATPase 2a and decreased insulin-mediated Akt-Ser473-phosphorylation in association with abnormal levels of epicardial fat tissue. Activin A, angiopoietin-2, and CD14-positive monocytes selectively accumulate in the diseased myocardium, resulting in reduced cardiomyocyte contractile function. At the same time, it is believed that these alterations in secretory products directly decrease the myocyte function via molecular changes, thus contributing to the development of coronary disease when certain comorbidities are associated.