Modern molecular biology technologies such as the generation of transgenic or gene-targeted rodent models have contributed tremendously to our understanding of the function of a large number of important genes involved in the regulation of appetite and energy homeostasis. Several different types of animal model have been employed in the study of the physiological and genetic basis of obesity, like models that reflect single gene mutations that have arisen spontaneously in rodent colonies and have subsequently been characterized. Another approach used is to speed up the random mutation rate artificially by treating rodents with mutagens or exposing them to radiation. The far greatest number of models however, consist of models that have disruption or over-expression of specific candidate genes in either a global fashion and from the germline or are restricted in both time and to certain tissue or cell types. Viral technologies on their own or in combination with various transgenic approaches represent an ever-increasing addition to the technologies used. Furthermore, rodents are no longer the only group of animals used for these studies and lower species like Drosophila or Zebra fish are also commonly used to screen for or characterise new players in this field. All different types of models a have advantages and disadvantages and there are still many gaps in our understanding of how body composition and energy storage are regulated, and a continuing need for the development of novel tools is required.