Transplant rejection, like tolerance, is a T cell-dependent event. There is compelling evidence to suggest that induction of transplant tolerance is an actively learned process in which T cells need to engage with the alloantigens in order to learn to tolerate the allograft. A family of cytokines whose receptors use the same IL-2 receptor γc chain (also called the common γc) plays an important role in regulating multiple aspects of the allograft response (I.e. Rejection vs. Tolerance). It is undeniable that γc cytokines can drive clonal expansion and effector maturation of alloreactive T cells, and therefore, targeting such cytokines or their receptor components remains an attractive way of blocking transplant rejection. However, we just started to appreciate that γc cytokines also regulate the acquisition of transplant tolerance via programming activated T cells for apoptotic cell death and via guiding the evolution of regulatory T cells. Thus, understanding precisely the role of γc cytokines in regulating T cell homeostasis and T cell regulation is critically important in the induction of transplant tolerance.