Whereas the importance of activating gene expression in metabolic pathways to control energy homeostasis is well established, the contribution of transcriptional inhibition is less well defined. In this review we highlight a crucial role of RIP140, a transcriptional corepressor for nuclear receptors, in the regulation of energy expenditure. Mice devoid of the RIP140 gene are lean, exhibit resistance to high-fat-diet-induced obesity, and have increased glucose tolerance and insulin sensitivity. Consistent with these observations, RIP140 suppresses the expression of gene clusters that are involved in lipid and carbohydrate metabolism, including fatty acid oxidation, oxidative phosphorylation and mitochondrial uncoupling. Therefore, the functional interplay between transcriptional activators and the corepressor RIP140 is an essential process in metabolic regulation.