A central goal immunologists has been to develop targeted therapies that will induce or maintain immunologic tolerance in the absence of potentially harmful immunosuppression. The ability to isolate and expand regulatory T-cell populations with immune suppressive activity will enable new forms of adoptive immunotherapy that may achieve this long held dream. Assuming that certain technical challenges regarding the manufacturing of regulatory T cells can be overcome, a wide variety of clinical applications can be envisioned using adoptively transferred CD4(+)CD25(+) regulatory T cells. It is likely that suppressor T cells will first be tested for their ability to prevent or treat graft-versus-host disease (GVHD) following allogeneic bone marrow or stem cell transplantation. A related approach will be clinical studies to induce allogeneic or xenogeneic tolerance using regulatory T cells in solid organ transplantation. A more technically challenging approach will be the use of regulatory T-cell therapy for autoimmune disorders. Finally on the horizon are approaches that will use genetically engineered lymphocytes to replace regulatory T cells in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and potentially to create more potent regulatory T (Treg) cells with enhanced suppressive activity.