Recent progress in the identification and functional analysis of protein kinases and adapter molecules that lead to activation of NF-kappaB family transcription factors has lead to a quite detailed understanding of one of the major signalling pathways that mediate a cell's response to environmental stress in a variety of host-defense situations. NF-kappaB is recognized as a key regulatory factor mediating the coordinate expression of genes which are part of the cellular machinery that functions to protect an organism against damage posed by physical, chemical or microbial noxae. In a wide variety of patho-physiological situations such as immune and inflammatory reactions, the expression of cytokines, interleukins and adhesion molecules in cells of the immune system including T and B cells, endothelial as well as phagocytic/antigen presenting cells is to a large extent regulated by NF-kappaB. Moreover, this transcription factor appears to play a central role in the regulation of apoptosis, an important cellular program that decides upon a cell's fate not only during embryonic development but also on its way from normal to the transformed phenotype. Thus, NF-kappaB has emerged also as an attractive target for therapeutic interference in a variety of pathological situations, including chronic inflammatory and autoimmune diseases, HIV infection and cancer.