The obesity epidemic is fast becoming one of the leading causes of mortality and morbidity worldwide. Over the past 30 years, gastrointestinal hormones have been increasingly understood to have an important role as regulators of appetite and energy balance in obese individuals. The levels of these hormones are modulated by bariatric surgery, and understanding how they are affected by such procedures can contribute to our comprehension of the underlying mechanisms by which these hormones affect obesity and its treatment. In this Review, we consider several gastrointestinal hormones that can contribute to obesity by modulating the activity of the gut-brain axis, and examine their specific effects on appetite, hunger and energy balance. Better understanding of the mechanisms by which these peptides exert their effects may enable the development of improved weight-loss medications and new treatments for obesity.