Research on the biological function of nuclear factor-kappaB (NF-kappaB), a key mediator of inducible transcription in the immune system, has traditionally focused on its role in the initiation of innate and adaptive immune responses. These studies have largely concentrated on the mechanisms of signalling that lead to NF-kappaB activation and on the positive role of NF-kappaB in both physiological immunity and pathological inflammation. More recently, there has been growing interest in the mechanisms that directly regulate the NF-kappaB transcriptional programmes. As a result, several new NF-kappaB regulatory components have been identified and some of the known components have been assigned new roles. In this Review, we discuss these new insights into the regulation of NF-kappaB.