Continuous immunosuppressive treatment allows the majority of transplant recipients to accept their donated organ and prevent acute graft rejection. However, life-long suppression of the immune system to respond appropriately to infectious, fungal, and carcinogenic threats coincides with substantial morbidity and mortality for the host. Thus for the past five decades research in the field of transplantation medicine has focused on innovative strategies to induce graft tolerance to donor alloantigens, a state in which the recipient's lymphocytes have learned to accept the foreign organ or tissue as "self" without the need of permanent immunosuppression. The fact that individuals of the same species attack each other's tissues can be explained with the set of specific antigens, designated as major histocompatibility antigens, which are expressed on each cell of the body and normally widely differ between nonrelated individuals. According to the genetic laws of transplantation, survival of allogeneic grafts is correlated with the number of differences among these histocompatibility antigens. An important exception to this rule can be observed in pregnant women who tolerate their unborn conceptus expressing a full set of nonmaternal antigens inherited by the father. The exact mechanisms of immune privilege exhibited by embryonic tissue during prenatal development have not yet been characterized in each detail. The field of maternofetal immunobiology has lately emerged as a new scientific branch in immunology which is gathering useful insights for future innovative tolerance strategies to prevent allogeneic graft rejection.