Food consumption is centrally and peripherally controlled by a core set of genes. Information on the control of feeding in mammals has blossomed after the identification of obesity genes such as ob, db and agouti whose function is well conserved between rodents and man. While energy homeostasis genes are conserved in all vertebrate species (from fish to amphibians and birds to mammals), less is known about their functional conservation. Some endophenotypes are clearly conserved and have helped utilize the respective strengths of different model species to drive scientific insight. However, the animal kingdom has evolved widespread behavioral adaptations to varying food niches and body sizes. Identifying the mechanisms underlying these differences will allow us to find nodes that can be modulated to ameliorate abnormal states or change growth parameters in all vertebrates, from commercially relevant food species to man. In the past decade, a lot of progress has been made in outlining the comparative basis of energy homeostasis in vertebrates. Here, we would like to present a current overview on the comparative endocrinology of energy homeostasis and its underlying neuroendocrinology with an emphasis on the insight this can give us into a) how and with what constraints energy homeostasis evolved and b) how energy homeostasis can be broken into endophenotypes that are translatable between species from fish to man.