Signal transduction events leading to the survival, differentiation, or apoptosis of cells of the innate or adaptive immune system must be properly coordinated to ensure the normal mounting and termination of immune responses. One of the key transcription factors in immune responses is nuclear factor κB (NF-κB), which has been the focus of intense investigation over the past two decades. With the identification of the CARMA1-BCL10-MALT1 complex and ongoing progress in understanding the molecular mechanisms connecting T cell and B cell receptor proximal signals to the IκB kinase (IKK) complex, a cohesive model of antigen receptor (AgR)-dependent signaling to NF-κB activation is beginning to emerge. In this review, we provide an overview of the current state of research into the mechanisms that regulate AgR-mediated NF-κB transcriptional activity, with particular focus on the events leading to activation of the IKK complex.