Transplantation tolerance can be achieved through several mechanisms, including the action of suppressor cells, the induction of anergy, or the deletion of graft-reactive donor T cells. In this article, the possible involvement of programmed cell death (apoptosis) in allograft rejection and transplantation tolerance is discussed. The recent characterization of members of the tumor necrosis factor-α gene family has identified ligands (Fas ligand and TRAIL) and corresponding death receptors (DR). In rejected organ transplants, apoptotic cells are frequently encountered. Conversely, high-level expression of Fas ligand on the allograft correlates with graft acceptance in some models of organ transplantation. Furthermore, some of the immunosuppressive drugs currently in clinical use might exert their activity at least in part through effects on apoptotic pathways. From the available data, it can be inferred that apoptosis contributes to the outcome after organ transplantation, being involved both in graft rejection and in transplantation tolerance.