The ability of apoptotic cells to serve as a source of alloantigen and to exert immune-regulatory effects on the innate and adaptive immune responses make apoptotic cell-based therapies a promising tool to down-regulate the anti-donor response that causes rejection of transplanted organs. Advances in understanding the mechanisms of interaction between apoptotic cells and antigen-presenting cells, including dendritic cells and macrophages, have provided the basis for the therapeutic harnessing of cells in the early stages of apoptosis to restrain the immune response or promote immunological tolerance. In this chapter, we compiled the available information on the mechanism(s) by which apoptotic cells interact with cells of the immune system and down-regulate the adaptive immune response, the effect of apoptotic cells on organ allograft survival in experimental models, and the potential application of apoptotic cell-based therapies for prevention or treatment of graft rejection and autoimmune disorders.