Brown adipose tissue is distinguished by its unique capacity for uncoupled mitochondrial respiration, which is highly regulated by sympathetic nerve activity. Because of this, energy expenditure in brown fat is capable of ranging over many orders of magnitude. The fact that the function of brown adipose tissue is impaired in obese rodents and that transgenic mice with decreased brown fat develop obesity demonstrates the importance of brown fat in maintaining nutritional homeostasis. However, the role of brown fat in humans is less clear. β3-Adrenergic receptors are found on brown adipocytes, and treatment with β3-selective agonists markedly increases energy expenditure and decreases obesity in rodents. Whether β3-selective agonists will be effective anti-obesity agents in humans is presently under investigation.