Nuclear hormone receptors are a large family of receptors that bind a wide range of lipolic hormones and intracellular ligands. They act as ligand-inducible transcription factors to regulate the expression of target genes and play important roles in normal development, reproduction, and metabolism. NRs bind to hormones steroids, thyroid hormone, and vitamin D as well as metabolites of fatty acids, cholesterol, and bild acids. Orphan receptors are another group of NRs for which no known ligands have been identified yet but appear to have major roles in regulating intracellular metabolism. Targeting NRs has been a major source for the development of new drugs, particularly selective agonists and antagonists for cancer and metabolic diseases. Additionally, hormone resistance syndromes in man have enlarged our understanding of the functions of specific NRs and their isoforms as well as genetic mechanisms for phenotype expression.