The gut and brain interact to control a host of behaviors including feeding, gut function, the perception of gastrointestinal malaise, and many autonomic responses. Most of these responses are mediated at the level of the brainstem, which also represents the site for many feeding-related actions of incretin-mimetic drugs that have revolutionized medicine. Understanding the systems that sense gut status and respond to incretin mimetics, as well as the defining circuits that process and relay these signals to promote specific behavioral and autonomic outputs may reveal potential targets for therapeutic intervention in obesity. This Keystone Symposia conference on the Gut-Brain Axis will provide a venue to learn about, discuss, and integrate the latest research advances regarding the sensing of information by the gut, the relay of this information to the brain, the mechanisms and circuits that mediate ensuing behavioral and physiologic changes, and the systems that mediate the anti-obesity actions of incretin-mimetics, as well as examining the integration of gut-brain signaling with islet biology. The conference will integrate academic and industry perspectives, providing the opportunity for interdisciplinary discussions that can drive therapeutic advances. More broadly, the conference will engage researchers from diverse areas—integrating neuroscience, gut biology, metabolism, behavior, physiology, nutrition, and pharmacology—allowing participants to comprehensively understand mechanisms of gut-brain communication and the importance of these mechanisms for physiology, pathophysiology, and therapy. This conference will also be held jointly with the Keystone Symposia conference on Islet Biology and Diabetes: Beta Cell Compensation, Failure and Recovery and will explore the emerging mechanisms and clinical insights that connect gut-brain communication with metabolic regulation that is central to islet cell biology and diabetes. Through shared keynote and joint scientific sessions, meals and poster sessions, participants will have an opportunity to network and share cross-disciplinary insights, encouraging innovative collaborations towards illuminating new biology and therapeutic avenues in these overlapping areas.