Adipocytes provide a model cell system for exploring the complexities of nuclear hormone receptor transcriptional regulation. Adipocytes produce lipid and cholesterol metabolites which can serve as activating ligands for many of the classic and "orphan" nuclear hormone receptors. At the same time, nuclear hormone receptors directly control adipocyte commitment. The recently described nuclear hormone receptor coactivators and corepressors provide an additional level of complexity to this system. This review emphasizes available in vitro and in vivo models and discusses them in the context of current controversies and future experimental directions.