G protein-coupled receptors (GPCRs) activate signaling pathways in the pancreas, skeletal muscle, the CNS and other tissues to regulate metabolism. This signaling is important in normal physiology, but its dysregulation can lead to diseases such as diabetes and obesity, which are the major contributing factors to cardiovascular disease. Talks in this session will address recently emerged unique and understudied aspects of G protein signaling in metabolism. The session will provide a unifying theme by which targeting novel aspects of GPCR signaling has the potential to be therapeutically relevant in diabetes and obesity.