Metabolic health is critically dependent on the dynamic control of processes such as energy balance and insulin sensitivity. This requires continuous communication across body systems, including the central nervous system. Hormones play a critical role as the circulating transmitters of the information required to co-ordinate these widely anatomically dispersed processes. This talk will focus on insights into the biology of three hormones, insulin, leptin (and its downstream melanocortin system) and GDF15 with a particular emphasis on what has been learned from the study of human disorders.