The nuclear factor-kappa B (NF-kappa B) signalling pathway serves a crucial role in regulating the transcriptional responses of physiological processes that include cell division, cell survival, differentiation, immunity and inflammation. Here we outline studies using mouse models in which the core components of the NF-kappa B pathway, namely the I kappa B kinase subunits (IKK alpha, IKK beta and NEMO), the I kappa B ;proteins (I kappa B alpha, I kappa B beta, I kappa B epsilon and Bcl-3) and the five NF-kappa B transcription factors (NF-kappa B1, NF-kappa B2, c-Rel, RelA and RelB), have been genetically manipulated using transgenic and knock out technology.