T cell-mediated immune responses to the grafted tissues are the major reason for failed organ transplantation. The regulation of T cell responses is complex and involves major histocompatibility complex molecules on transplanted organs, cytokines, regulatory cells, and antigen-presenting cells. The evolutionary conserved Wnt signal transduction pathway has long been known for its importance in development of stem cells and immature T cells in the thymus. Recent evidence indicates the Wnt pathway as a master regulator of T cell immune responses via governing the balance between T helper 17/regulatory T cells and by regulating the formation of effector and memory cytotoxic CD8 T cell responses. In doing so, Wnt signals influence the outcome of immune responses in transplantation settings.