Body weight is determined by the balance between energy intake and energy expenditure. Obesity ensues when energy intake exceeds that of energy expenditure. To date, the majority of pharmaco-therapies to control body weight have been directed towards the appetitive limb of this energy balance equation. Very few anti-obesity agents target the manipulation of energy expenditure. The recent unequivocal demonstration that functional brown adipose tissue is present in adult humans has sparked a great deal of interest in developing means to exploit thermogenesis to control body weight. Thermogenesis is defined as the dissipation of energy through the production of heat and occurs in specialised tissues including brown adipose tissue and skeletal muscle. This chapter will highlight a number of animal models that are currently utilised in effort to understand the mechanisms that underpin thermogenesis. It will describe the control of thermogenesis in skeletal muscle and adipose tissue as well as detailing the role of thermogenesis in determining the susceptibility to obesity in a number of distinct animal models.