The worldwide obesity epidemic represents a severe threat to global health and is driving the scientific quest for a greater understanding of the mechanisms that regulate bodyweight, in order to develop effective preventative and therapeutic strategies. These research efforts have identified gut hormones as key regulators of energy and glucose homeostasis and have implicated them in the pathogenesis of obesity, the weight recidivism that frequently plagues dietary interventions and the marked changes in eating behaviour, weight reduction and metabolic benefits that accompany bariatric surgery. Consequently, therapeutic strategies aimed at modulating gut hormone levels or targeting their receptors are now being used to treat people with obesity and obesity-associated diseases, such as type 2 diabetes, and represent the most promising therapeutic avenue to combat the obesity epidemic.