The tumor necrosis factor (TNF) superfamily consists of a wide variety of proteins, some cell-bound and others secreted, that regulate many cellular processes. In particular, TNF-family proteins regulate the life and death not only of tumor cells, but of activated cells of the immune system. This overview discusses the six known mammalian TRAF proteins, of which TRAF1, 2, 3, 5, and 6 have been shown to interact directly or indirectly with members of the TNFR superfamily. Structural features of TRAF proteins are described along with a discussion of TRAF-interacting proteins and the signaling pathways activated by TRAF proteins. Finally, a discussion is provided on the phenotypes of TRAF-knockout mice.