The NF-κB family of transcription factors plays a crucial role in the immune, inflammatory and apoptotic responses. These proteins are normally found in the cytoplasm, retained by interaction with an inhibitory molecule called IκB. Activation of the NF-κB signalling cascade results in phosphorylation and degradation of IκB, allowing nuclear translocation of the NF-κB complexes. The recent identification of a high-molecular-weight complex containing two kinases and a regulatory subunit has led to a flurry of new results that shed light on some of the most complex mechanisms contributing to the exquisite regulation of NF-κB activity.