Energy expenditure through brown adipose tissue thermogenesis contributes either to maintenance of body temperature in a cold environment or to wasted food energy, i.e. cold-induced or diet-induced thermogenesis. Both mechanisms are due to a specific and unique protein: the uncoupling protein-1. Uncoupling protein-1 is exclusively expressed in mitochondria of brown adipocytes where it uncouples respiration from ATP synthesis, dissipating the proton gradient as heat. In humans, although uncoupling protein-1 can be detected, the inability to quantify brown adipose tissue makes it difficult to argue for a role for uncoupling protein-1 in thermogenesis and energy expenditure. This review summarizes data supporting the existence of brown adipocytes and the role of UCP1 in energy dissipation in adult humans. Understanding the mechanisms which regulate transcription and expression of the human UCP1 gene will facilitate the identification of molecules able to increase the levels of this protein in order to modulate energy expenditure in adult humans.