Nuclear factor (NF)-κB and inhibitor of NF-κB kinase (IKK) proteins regulate many physiological processes, including the innate- and adaptive-immune responses, cell death and inflammation. Disruption of NF-κB or IKK function contributes to many human diseases, including cancer. However, the NF-κB and IKK pathways do not exist in isolation and there are many mechanisms that integrate their activity with other cell-signalling networks. This crosstalk constitutes a decision-making process that determines the consequences of NF-κB and IKK activation and, ultimately, cell fate.