A constant body temperature can only be maintained when the rate of heat dissipation equals the rate of heat loss. Thermoregulatory heat production mechanisms compensating heat loss are classically categorized as shivering and non-shivering thermogenesis. Non-shivering thermogenesis occurs in brown adipose tissue, a unique heat producing organ only found in mammals. In brown adipose tissue mitochondria, the proton motive force across the inner membrane is dissipated as heat rather than converted to ATP. This tightly regulated process is catalyzed by the uncoupling protein 1. Non-shivering thermogenesis is elicited by the sympathetic innervation from hypothalamic and brain stem control regions which are activated by cold sensation. In a cold environment up to half of the metabolic rate of rodents can be attributed to non-shivering thermogenesis in brown adipose tissue. The high thermogenic capacity of brown adipose tissue recruited in the defense of normothermia may also play a role in the regulation of energy balance in the face of hypercaloric nutrition. In this light, the discovery of significant amounts of metabolically active brown adipose tissue in healthy adult humans reintroduces an old player in human energy balance research and may enable new strategies to prevent excess body fat accumulation in man.