The nuclear receptor superfamily and the transcriptional factors associated with cytokines are inherentlydifferent families of signaling molecules and activate gene transcription by binding to their respectiveresponsive element.However,it has become increasingly clear from our works and others that nuclearreceptors are important regulators of cytokine production and function through complex and variedinteractions between these distinct transcriptional factors.This review provides a general overview of themechanism of action of nuclear receptors and their transcriptional crosstalk with transcriptional factorsassociated with cytokine transduction pathways.One of the most important mechanistic aspects is protein toprotein interaction through a direct or co-regulator-mediated indirect manner.Such crosstalk is cruciallyinvolved in physiological and therapeutic roles of nuclear receptors and their iigands in immunity,inflammation and cytokine-related tumors.Cellular & Molecular Immunology.2004;1(6):416-424. The nuclear receptor superfamily and the transcriptional factors associated with cytokines are inherently different families of signaling molecules and activate gene transcription by binding to their corresponding responsive elements. However, it has become increasingly clear from our works and others that nuclear receptors are important regulators of cytokine production and function through complex and variedinteractions between these distinct transcriptional factors. This review provides a general overview of the themechanism of action of nuclear receptors and their transcriptional crosstalk with transcriptional factors associated with cytokine transduction pathways. One of the most important mechanistic aspects is protein toprotein interaction through a direct or co-regulator-mediated indirect manner. Suc crosstalk is cruciallyinvolved in physiological and therapeutic roles of nuclear receptors and their iigands in immunity, inflammation and cytokine-related tumors. Cellular & Molecular Immunology. 20 04; 1 (6): 416-424.