Nuclear receptors are ligand-activated transcription factors and include the receptors for steroid hormones, lipophilic vitamins, sterols, and bile acids. These receptors serve as targets for development of myriad drugs that target a range of disorders. Classically defined ligands that bind to the ligand-binding domain of nuclear receptors, whether they are endogenous or synthetic, either activate receptor activity (agonists) or block activation (antagonists) and due to the ability to alter activity of the receptors are often termed receptor "modulators." The complex pharmacology of nuclear receptors has provided a class of ligands distinct from these simple modulators where ligands display agonist/partial agonist/antagonist function in a tissue or gene selective manner. This class of ligands is defined as selective modulators. Here, we review the development and pharmacology of a range of selective nuclear receptor modulators.