Obesity is the most common metabolic disease globally. It is increasingly a problem of children and individuals in poor countries characterized by food insecurity. This is of great concern as childhood obesity predicts increased future adult obesity. To curb the epidemic of obesity, it is essential to understand the regulation of appetite. Energy stores and nutrient homeostasis are maintained by hypothalamic regulation of energy balance. The hypothalamus receives neural and endocrine signals from the gut, adipose tissue and pancreas in response to food intake. These are integrated, interpreted and directed to other centers in the brain and peripheral organs to orchestrate energy homeostasis. This brain-gut axis is disrupted in obesity. This review discusses the various hormones involved in the regulation of energy balance both at the level of the gut and in the central nervous system.