The incidence of obesity and associated metabolic disorders increase worldwide. Accumulating evidence points towards nuclear receptor (NR) transcription factors as potential treatment targets. The retinoic acid-related orphan receptor α (RORα) is a NR that has been implicated in the regulation of a wide variety of metabolic pathways. Molinaro et al. generated a liver-specific RORα deficient mouse strain that was metabolically phenotyped on both chow and western-style diet (WSD). Their data show that the deletion of RORα in the liver does not affect glucose or lipid metabolism during WSD in mice. Further studies testing the role of liver RORα or the double RORα and RORγ deletion in different dietary settings are needed to further elucidate the role of RORα in obesity and metabolic disorders.