All multi-cellular organisms protect themselves from invasion by allogeneic organisms and cells by mounting immune responses. While protective, allogeneic immune responses present a threat to successful reproduction in eutherian mammals in which the maternal immune system is exposed to the semi-allogeneic fetus. Thus, successful reproduction in eutherian mammals depends on mechanisms that control the potentially hostile maternal immune system without hindering immune responses to potentially deadly infectious organisms. Three general mechanisms have been proposed to explain successful reproduction in mammals: (i) the formation of an anatomical barrier between mother and fetus; (ii) expression of allogeneic antigens at a very low level by the fetus; and (iii) hindrance of the maternal immune system responding to fetal antigens. These mechanisms explain in part how the fetus evades the maternal immune system; however, they do not explain fully the survival of the fetus. We hypothesize that site-specific immune suppression may play an important role in successful eutherian reproduction in conjunction with other mechanisms. Site-specific immune suppression at the fetal-maternal interface would protect the fetus while allowing peripheral maternal immune responses to continue unabated.