Oxyntomodulin, a product of the proglucagon gene, is released from the enteroendocrine L-cells of the gastrointestinal tract after the digestion of food, and acts via glucagon-like peptide 1 receptors in the arcuate nucleus to induce satiety. The administration of oxyntomodulin to animals and humans causes weight loss by reducing food intake in combination with increasing energy expenditure. Thus, the development of potent and long-acting analogs of oxyntomodulin is an exciting new therapeutic avenue for addressing the global obesity epidemic. This review discusses the role of oxyntomodulin in the physiological control of appetite, and presents the currently available evidence suggesting its potential as an obesity treatment.