Sertoli Cells (SCs) in the testes have evolved to possess unique immune privileged properties to protect the developing germ cells from immunological attack. These immune privileged properties are not restricted to the testis, as SCs survive when transplanted across immunological barriers as allo- and xeno-grafts. Here we discuss the therapeutic potential of transplanted SCs in protecting cells, tissues or organs, which could be paramount in the field of transplantation to treat lifethreatening diseases. Similar to the testis, transplanted SCs inhibit and/or modulate the immune response locally (at the transplant site) or systemically. Protection of transplanted cells, present in close vicinity of SCs, along with reduction of inflammation at the transplant site support that SC can inhibit and/or modulate the immune response locally. While protection of skin, islets in the contralateral kidney, and organs by SCs support their role in inducing systemic tolerance. Additionally, amelioration of autoimmune diseases, specifically type 1 diabetes mellitus, further supports this notion. Studies exploring SCs role as a vehicle for the cell based gene therapy further widens the horizon of SCs therapeutic potential in transplantation.