Successful allogeneic hematopoietic stem cell transplantation (HSCT) and solid organ transplantation require development of a degree of immune tolerance against allogeneic antigens. T lymphocytes play a critical role in allograft rejection, graft failure, and graft-versus-host disease (GVHD). T-cell tolerance occurs by two different mechanisms: (1) depletion of self-reactive T cells during their maturation in the thymus (central tolerance), and (2) suppression/elimination of self-reactive mature T cells in the periphery (peripheral tolerance). Induction of transplant tolerance improves transplantation outcomes. Adoptive immunotherapy with immune suppressor cells including regulatory T cells, natural killer (NK)-T cells, veto cells, and facilitating cells are promising therapies for modulation of immune tolerance. Achieving mixed chimerism with the combination of thymic irradiation and T-cell-depleting antibodies, costimulatory molecule blockade with/without inhibitory signal activation, and elimination of alloreactive T cells with varying methods including pre- or post-transplant cyclophosphamide administration appear to be effective in inducing transplant tolerance.