Transplantation of stem cells into the preimmune fetal environment to treat congenital disorders or to achieve donor-specific tolerance is a very potent treatment strategy. The fetal lamb model is the animal model that has given most experimental support for fetal stem cell transplantation to date. Potential beneficial effect of in-utero transplantations (IUT) are proven in several animal models. Transplanting human fetal mesenchymal stem cells (MSCs) in utero to mice suffering from osteogenesis imperfecta shows great effect with reduction of fractures and increased bone strength, thickness, and length, and also improvements in multiscale tissue properties. Human MSCs can be isolated from fetal tissues such as the first and second trimester blood, liver, bone marrow, and lung. The discovery of human stem cells has laid the foundation for a rapid development regarding clinical stem cell transplantations. The most successful group of patients transplanted in utero is the group of fetuses with immunodeficiencies.