It is speculated that presentation of self-peptides to autoreactive T cells normally results in T cell tolerance. In autoimmune conditions, breakdown in the tolerization process results in activation of self-reactive T cells and an immune attack on host tissues. Our understanding of the immune cells and signaling pathways that contribute to this breakdown in T cell tolerization mechanisms is beginning to be deciphered. In particular, the elucidation of the mechanisms that contribute to the release of host antigen, the identification of the antigen-presenting cells that present the host peptides to self-reactive T cells and the role of members of the tumor necrosis factor receptor/ligand families that contribute to inappropriate activation of self-reactive T cells is advancing. The accumulating data from these studies will hopefully provide new ideas for combating autoimmunity.