Nuclear Factor-Kappa B (NF-kappa B) was first identified by Sen and Baltimore (1986, Cell 46, 705-716) as a constitutively active transcription factor binding the kappa light chain immunoglobulin enhancer in B cells. Shortly afterwards, the same researchers found NF-kappa B to be present in other cell types in an inactive cytoplasmic form which upon cellular stimulation could be induced to translocate to the nucleus and bind DNA. Subsequently, it has been demonstrated that NF-kappa B performs a critical role as a regulator of the immune system, the response to stress, apoptosis, viral replication and is involved in many diseases, leading to it becoming one of the most intensively studied transcription factors of the last decade. The pivotal role played by NF-kappa B is illustrated not only by the great diversity of genes that it regulates, but also by the large variety of stimuli leading to its activation. This article will address how NF-kappa B, a ubiquitously expressed transcription factor composed of dimers formed from five subunits, differentially regulates the expression of such a diverse array of genes with different functions, in different cell types and at different times. Recent research indicates that this behavioral diversity arises from a delicately balanced network of protein: protein interactions: NF-kappa B activity is determined not only through its regulated nuclear localization but is also dependent on the cellular context in which it is found.