Epicardial fat (EAT), the visceral fat of the heart, is highly enriched in genes involved in inflammation and lipid metabolism; it activates local and systemic inflammation and innate inflammatory response. EAT is rich in saturated fatty acids and has high protein content, and the greatest capacity for free fatty acids release and uptake among any other visceral fat depots. Of interest, EAT is highly enriched in sphingolipids, including ceramide. EAT clinical measurability with an ultrasound technique, first developed and validated by Iacobellis, and its rapid responsiveness and reduction to medications targeting the visceral fat, such as the glucagon-like peptide 1 analogues (GLP1A), as ongoing clinical trials are demonstrating, is of growing and remarkable interest.