The nuclear receptor superfamily contains important transcriptional regulators that play pleiotropic roles in cell differentiation, development, proliferation, and metabolic processes to govern liver physiology and pathology. Many nuclear receptors are ligand-activated transcription factors that regulate the expression of their target genes by modulating transcriptional activities and epigenetic changes. Additionally, the protein complex associated with nuclear receptors consists of a multitude of coregulators, corepressors, and noncoding RNAs. Therefore, acquiring new information on nuclear receptors may provide invaluable insight into novel therapies and shed light on new interventions to reduce the burden and incidence of liver diseases. (Hepatology Communications 2018;2:765-777).