Epicardial adipose tissue has unique properties that distinguish it from other depots of visceral fat. Rather than having distinct boundaries, the epicardium shares an unobstructed microcirculation with the underlying myocardium, and in healthy conditions, produces cytokines that nourish the heart. However, in chronic inflammatory disorders (especially those leading to heart failure with preserved ejection fraction), the epicardium becomes a site of deranged adipogenesis, leading to the secretion of proinflammatory adipokines that can cause atrial and ventricular fibrosis. Accordingly, in patients at risk of heart failure with preserved ejection fraction, drugs that promote the accumulation or inflammation of epicardial adipocytes may lead to heart failure, whereas treatments that ameliorate the proinflammatory characteristics of epicardial fat may reduce the risk of heart failure. These observations suggest that epicardial adipose tissue is a transducer of the adverse effects of systemic inflammation and metabolic disorders on the heart, and thus, represents an important target for therapeutic interventions.