ABSTRACT: Corepressors are large proteins that facilitate transcriptional repression through recruitment of histone-modifying enzymes. Two major corepressors, SMRT (silencing mediator for retinoid and thyroid hormone receptors) and N-CoR (nuclear receptor corepressor), have been shown to mediate repression associated with nuclear receptors and a myriad of other transcription factors. This review will focus on recent studies on these proteins, including newly discovered physiological roles of the corepressors, their modes of regulation, their roles in antiestrogen-resistant breast cancer and their functions during the cell cycle.