Studies indicating an important role of the TNF-receptor family in control of cell proliferation, differentiation, and death have drastically increased in number in recent years. The main function of many members of this family is cell death triggering, and this is apparently the only function for some of them. Studies on the molecular mechanisms of cell death activated by members of the TNF-receptor family revealed and identified proteins directly or indirectly associated with TNF receptors. Pathways of cytotoxic signal transduction by some members of the TNF-Rs family based on currently proven protein-protein interactions and the role of distinct proteins in these processes are summarized in this review.