Nuclear receptors (also known as nuclear hormone receptors) are hormone-regulated transcription factors that control many important physiological and developmental processes in animals and humans. Defects in receptor function result in disease. The diverse biological roles of these receptors reflect their surprisingly versatile transcriptional properties, with many receptors possessing the ability to both repress and activate target gene expression. These bipolar transcriptional properties are mediated through the interactions of the receptors with two distinct classes of auxiliary proteins: corepressors and coactivators. This review focuses on how corepressors work together with nuclear receptors to repress gene transcription in the normal organism and on the aberrations in this process that lead to neoplasia and endocrine disorders. The actions of coactivators and the contributions of the same corepressors to the functions of nonreceptor transcription factors are also touched on.