The transcription factor NF-kappaB has a central role in coordinating the expression of a wide variety of genes that control the immune system. Defining the proteins and the mechanisms that transmit signals from the T-cell receptor to NF-kappaB is therefore an important goal for immunologists. Although most players have probably been identified, relatively little is known about the detailed molecular mechanisms involved in the cascade leading to NF-kappaB activation following engagement of the T cell receptor by a foreign antigen. PKCtheta, CARMA1, BCL-10, MALT1 and caspase 8 are signalling proteins that have a key role in antigen receptor-mediated lymphocyte activation through the NF-kappaB pathway. In this review, we discuss recent insights into this specific signal transduction cascade, and the way it is regulated. Several lines of evidence, mainly from biochemical studies of T cells clearly indicate that phosphorylation, ubiquitination and degradation are key control elements in the positive and negative regulation of the NF-kappaB pathway in response to TCR stimulation.