It is not clear why on treatment with certain killer cytokines or chemotherapeutic agents, some cells undergo apoptosis while others do not. The delineation of sensitivity/resistance pathways should provide a more specific therapy for cancer and other hyperproliferative diseases. Most cells die either by apoptosis or by necrosis. The biochemical pathway that mediates these two modes of cell death has recently been described. The nuclear factor (NF)-kappa B and the genes regulated by this transcription factor have been shown to play a critical role in induction of resistance to killer agents. Thus, inhibitors of NF-kappa B activation have a potential in overcoming resistance to apoptosis induced by various agents. The evidence for and against such a notion is discussed.