The nuclear receptor (NR) superfamily comprises approximately 50 members that are responsible for regulating a number of physiologic processes in humans, including metabolism, homeostasis, and reproduction. Included in the superfamily are the receptors for steroids, lipophilic vitamins, bile acids, retinoids, and various fatty acids. NRs exert their action as transcription factors that directly bind to the promoters of target genes and regulate their rate of transcription. To modulate transcription, however, NRs must recruit a number of accessory coregulators known as corepressors and coactivators. These coregulators harbor a variety of activities, such as the ability to modify chromatin structure, interact with basal transcriptional machinery, and modify RNA splicing. Recent studies have revealed that the pharmacological characteristics of various NR ligands are regulated by their ability to modulate the coregulator interaction profile of an NR.