Free fatty acids (FFAs) have been demonstrated to act as ligands of several G-protein-coupled receptors (GPCRs). GPR120 is activated by unsaturated long-chain FFAs and has a crucial role in various physiological homeostasis mechanisms such as incretin hormone secretion and adipogenesis. Recent studies showed that a lipid sensor GPR120 has a key role in sensing dietary fat and in the control of energy homeostasis in both humans and rodents. Dysfunction of GPR120 is identified as a novel risk factor for diet-induced obesity. In this review, I provides recent development in the field and discusses its physiological roles and potential as drug targets.