In mammals living within the thermoneutral zone basal heat production is sufficient to compensate for heat loss and defend a drop in body temperature. Moving to ambient temperatures below this zone the thermal conductance is decreased to a minimum and thermoregulatory heat production is activated to compensate for increased heat loss. In small mammals two mechanisms, nonshivering thermogenesis in brown adipose tissue and shivering in skeletal muscle, contribute to thermoregulatory heat production. Nonshivering thermogenesis in brown adipose tissue is based on the unique capacity of brown adipocyte mitochondria to dissipate proton motive force as heat without ATP synthesis. This process is catalyzed by the mitochondrial carrier Uncoupling Protein 1 (UCP1) (for review see (1)). Non-UCP1-mediated mechanisms for nonshivering thermogenesis in tissues other than brown adipose tissue have been suggested, but their physiological relevance and biochemical mechanisms are not clear. The power for nonshivering thermogenesis in brown adipose tissue is around 160 mW/g at thermoneutrality and attains up to 330 – 480 mW/g in the cold (reviewed in (2)). This recruitment of heating power in the cold, also termed adaptive thermogenesis, is mainly accomplished by hyperplastic growth of brown adipose tissue, acceleration of mitochondrial biogenesis in brown adipocytes, and increased UCP1 synthesis. Moreover, angiogenesis improves blood supply to fuel high metabolic rate and to distribute the heat in the body. This dynamic remodelling is controlled by the sympathetic innervation of brown adipose tissue. In the control of adaptive thermogenesis in brown adipocytes adrenergic signaling pathways target complex transcriptional machineries composed of nuclear hormone receptors, cAMP response element binding proteins and coactivators. However, the cell-type specificity of these transcriptional responses are far from being understood. A brown adipocyte specific enhancer has been well characterised in the Ucp1 gene (1), and most recently our laboratory has identified another enhancer in the Ucp3 gene conveying brown adipocyte specific gene transcription (unpublished data). Further analysis of the transcription factor modules and epigenetic modifications at such cis regulatory genomic enhancer regions will help to understand the molecular basis of adaptive thermogenesis. Endocrine or paracrine mediators such as prostaglandins, bile acids, natriuretic peptides and fibroblast growth factors may also contribute to recruitment, either downstream or parallel to neuronal adrenergic signaling. The physiological relevance of these factors in the context of cold acclimation is not clear. In mice acclimated to thermoneutrality, acute cold exposure elicits strong shivering as the capacity for nonshivering thermogenesis is low and not sufficient to defend normothermia. During prolonged exposure for several days shivering is subsequently replaced by nonshivering thermogenesis. In fact cold acclimated rodents refrain from shivering unless their maximal power for nonshivering thermogenesis approaches exhaustion. A major question is whether this recruitment of thermogenic heating power can be completely ascribed to the recruitment of thermogenic capacity in brown adipose tissue. To address this question we compared the maximal cold induced heating power (HPmax) of wildtype and UCP1 ablated C57BL/6J mice, including basal metabolic rate, shivering and nonshivering thermogenesis (3). All mice were preacclimated to moderate cold at 18°C before acclimation to 5°C. In wildtype mice acclimated close to thermoneutrality (27°C) HPmax was 757 mW, but increased to ~1230 mW (+473 mW) after cold acclimation whereas in UCP1-KO mice HPmax had increased from 714 mW to 941 mW (+227 mW). This reduction of adaptive thermogenesis by 52 % in UCP1-KO mice underlines the important role of brown adipose tissue for improved cold resistance. However, this observation also demonstrates that significant recruitment of additional heating power can occur in the absence of functional brown adipose tissue. In white adipose tissues of cold acclimated UCP1-KO mice the mitochondrial density, the activity of cytochrome c oxidase and the expression of the brown adipocyte marker CIDEA are increased as compared to wildtype (3). The trigger and the utility of this remodeling is unclear but the extra metabolic power in white adipose tissue may contribute to adaptive thermogenesis in UCP1-KO mice.