Serotonin has been around for a while as a paracrine signal in the islet. Recent studies point to a role of serotonin mainly, if not exclusively, under conditions of increased metabolic demand, such as obesity and pregnancy. We now show that serotonin is produced and released from human beta cells to inhibit neighboring alpha cells. The cartoon illustrates what we think serotonin is doing in the human islet. Serotonin may turn out to be the major signal that mediates the inhibition of alpha cell secretion of glucagon during conditions of elevated glycemia.