In utero hematopoietic stem cell transplantation is an entirely nonmyeloablative approach to achieve mixed hematopoietic chimerism and associated donor-specific tolerance. This chapter provides the rationale and methodologic detail for the administration of stem cells to the "preimmune" mouse fetus by a variety of routes. The development of murine model systems for in utero transplantation has accelerated progress in the field of in utero hematopoietic stem cell transplantation. Creative use of these models should also have experimental application to the fields of fetal gene therapy, stem cell biology, and developmental biology.