Since NF-κB activation is so crucial to many cellular processes, a tight regulation of the NF-κB signalling pathway and the genes it induces is an absolute requirement to fine-tune the inflammatory response. Moreover, terminating an NF-κB response is essential to prevent persistent NF-κB activation that may lead to chronic inflammation and/or tumorigenesis. To achieve this, cells employ different mechanisms, including the expression of inhibitory proteins that downregulate NF-κB signalling [32]. Below we give an overview of a number of proteins that are involved in the dampening or termination of the NF-κB response, some of them under the control of NF-κB itself and thus acting in a negative feedback loop. In addition, we discuss the potential role of these NF-κB inhibitory factors in the immunopathology of RA. Several other proteins involved in the negative regulation of NF-κB-dependent inflammatory responses, such as MyD88s, IRAK-M, and TOLLIP, have been described (reviewed in [33]). These proteins are not discussed here, since a link with RA pathology has not yet been reported.