Novel therapies that focus on regulating appetite are a new area of hope in the treatment of obesity and metabolic disorders. By emphasizing the emerging relationships between the gut, brain and hormone systems, the objective of such therapies is to more finely tune the processes behind hunger and satiety. Innovations in pharmacotherapy, including GLP-1 receptor agonists, dual and triple hormone agonists and neuroendocrine modulators are changing the clinical landscape for weight management. Beyond pharmacotherapy, studies of the microbiome, gene expression, and neural circuits offer alternative pathways for appetite regulation and energy balance. When combined with lifestyle therapies, there is increased potential for long-term effectiveness and sustainability. This session will highlight the most recent discoveries, mechanisms of action and clinical outcomes of new appetite-regulating therapies that are evolving the way we think about treating obesity and consideration for preventive medicine.