Since publication of the initial chapter on animal models in 1998 (1), there has been an explosive increase in the number of animal models in mice. This has arisen from two major avenues of research-the use of transgenic and gene-targeting approaches for proof of function for several genes that were thought to alter energy balance or through the use of similar approaches to study genes that had not previously been associated with obesity but in which a phenotype of altered body composition and/or food intake has emerged. These genes (Table 1) have a wide range of functions including eﬀects on food intake, energy expenditure and physical activity, tissue metabolism, and adipose tissue diﬀerentiation. Further important developments have been the identiﬁcation of the tub gene as an insulin-signaling molecule expressed in the nervous system and the elucidation of the signaling pathways associated with leptin activation of its long form of receptor in the hypothalamus. Thus, the identity of all of the spontaneous single gene mutations that cause obesity is now known. While these models were a major focus of the previous review, this chapter will concentrate on new information that has been published in the interim period. Readers are referred to the original chapter (1) and other chapters in the present edition of the Handbook of Obesity for more detailed information on the single gene models and other nonrodent models of obesity.