Members of the nuclear receptor family are involved in an increasing number of processes in the cell. These receptors can directly regulate gene expression by binding to DNA. The molecular basis for transcriptional activation is so far not well understood. Nevertheless, in the past years, the identification of cofactors has brought some new insight. These molecules can either enhance or repress the transcriptional activity of nuclear receptor. If the nuclear receptor or the cofactor carries a mutation that prevents the interaction between the two partners, signal transduction can be interrupted. Moreover, the possibility to interact with different nuclear receptors or other transcription factors confers to cofactors a pivotal role in the integration of different transduction pathways in the cell. Besides, these cofactors provide a model to explain the action in vivo of some nuclear receptor antagonists. It is evident that the identification of new cofactors as well as the study of their mode of action will soon allow rapid progress in the comprehension of cellular growth and differentiation. Moreover, these cofactors should soon constitute new therapeutic targets