Immune-suppressive cellular immunotherapy requires large numbers of antigen-specific regulatory T cells (T(reg) cells), lymphocytes that suppress certain immune responses. Together, three papers in this issue of Science Translational Medicine describe protocols for the ex vivo expansion of human T(reg) cells and assess the immune-suppressive function of ex vivo-manipulated T(reg) cells after transfer into humanized mouse disease models. Along with recent phase I clinical trial results, these new data provide a platform for clinical use of T(reg) cells as personalized therapeutic agents for the treatment of autoimmune diseases, graft-versus-host disease, and transplant rejection.