Obesity and diabetes are strongly associated with metabolic and cardiovascular disorders including dyslipidemia, coronary artery disease, hypertension, and heart failure. Adipose tissue is identified as a complex endocrine organ, which by exerting a wide array of regulatory functions at the cellular, tissue and systemic levels can have profound effects on the cardiovascular system. Different terms including "epicardial," "pericardial," and "paracardial" have been used to describe adipose tissue deposits surrounding the heart. Epicardial adipose tissue (EAT) is a unique and multifaceted fat depot with local and systemic effects. The functional and anatomic proximity of EAT to the myocardium enables endocrine, paracrine, and vasocrine effects on the heart. EAT displays a large secretosome, which regulates physiological and pathophysiological processes in the heart. Perivascular adipose tissue (PVAT) secretes adipose-derived relaxing factor, which is a "cocktail" of cytokines, adipokines, microRNAs, and cellular mediators, with a potent effect on paracrine regulation of vascular tone, vascular smooth muscle cell proliferation, migration, atherosclerosis-susceptibility, and restenosis. Although there are various physiological functions of the EAT and PVAT, a phenotypic transformation can lead to a major pathogenic role in various cardiovascular diseases. The equilibrium between the physiological and pathophysiological properties of EAT is very delicate and susceptible to the influences of intrinsic and extrinsic factors. Various adipokines secreted from EAT and PVAT have a profound effect on the myocardium and coronary arteries; targeting these adipokines could be an important therapeutic approach to counteract cardiovascular disease.