The significant burden of overweight and obesity on our society necessitates the development of lifestyle strategies that facilitate successful long-term body weight management. Recently, the discovery of novel cellular modulators of the brain-gut axis have generated much interest in possible therapeutic manipulation of these and other hormones that regulate energy intake. These modulators include the enterohormones ghrelin, peptide YY 3-36, and cholecystokinin, and the adipocyte-derived hormone leptin. There is some evidence that dietary macronutrient composition can influence concentrations of these hormones, which could impact sensations of hunger, satiety, and ultimately energy intake. The purpose of this review is to provide background information on these four peripheral hormones involved in energy intake regulation, to discuss what is currently known about their mechanism of action, and to present research findings related to the effect of macronutrient composition on concentrations and efficacy of these hormones. Potential applications of this information are also discussed.