Transcriptional control of cellular energy metabolic pathways is achieved by the coordinated action of numerous transcription factors and associated coregulators. Several members of the nuclear receptor superfamily have been shown to play important roles in this process because they can translate hormonalnutrientand metabolite signals into specific gene expression networks to satisfy energy demands in response to distinct physiological cues. Estrogen-related receptor (ERR) alphaERRbetaand ERRgamma are nuclear receptors that have yet to be associated with a natural ligand and are thus considered as orphan receptors. Howeverthe transcriptional activity of the ERRs is exquisitely sensitive to the presence of coregulatory proteins known to be essential for the control of energy homeostasisand for all intents and purposesthese coregulators function as protein ligands for the ERRs. In particularfunctional genomics and biochemical studies have shown that ERRalpha and ERRgamma operate as the primary conduits for the activity of members of the family of PGC-1 coactivators. As transcription factorsthe ERRs control vast gene networks involved in all aspects of energy homeostasisincluding fat and glucose metabolism as well as mitochondrial biogenesis and function. Phenotypic analyses of knockout mouse models have shown that all three ERRs are indispensable for proper development and/or survival of the organism when subjected to a variety of physiological challenges. The focus of this review is on the recent and rapid advances in understanding the functions of the ERRs in regulating bioenergetic pathwayswith an emphasis on their roles in the specification of energetic properties required for cell- and tissue-specific functions.