The idea of using organ transplantation to solve quality-of-life issues was first introduced a century ago, with cornea transplants and thrusted before the world again in 1998, following a controversial hand transplant. Uterus transplantation (UTn) has been proposed as another quality-of-life transplant for the cure of permanent uterine factor infertility. In order to proceed in humans, a greater appreciation of the immunological mechanisms that underlie UTn is desirable. Allogeneic UTn (animal model) was first described by 2 studies in 1969. The first and only human UTn, performed in 2000, was an early attempt with limited use of animal model experiments prior to moving onto the human setting. Since then, work using rat, mouse, ovine, goat, and nonhuman primate models has demonstrated that the uterus is a very different but manageable organ immunologically compared to other transplanted organs. Therefore, specifically exploring immunological issues relating to UTn is a valuable and necessary part of the inevitable scientific process leading to successful human UTn.