Pregnancy and autoimmune disorders (ADs) coexist in a delicate balance. Whereas women are disproportionately affected by ADs--frequently occurring during reproductive years--the disease often improves during pregnancy, unless severe. However, when ADs are at an advanced stage, both mother and fetus can be severely affected. Maternal AD amelioration reduces fetal morbidity/mortality. AD improvement occurs without compromising immune tolerance for the fetus; however, it is short-lived since postpartum, flare-up frequently occurs. Consequences of pregnancy-related maternal disease can have life-long impact. Pregnancy is not an immune-suppressed state, but rather a controlled inflammatory environment with distinct local and systemic coordination. Pregnancy requires a delicate immune balance; the embryo/allograft does not cause graft-versus-host disease while the mother/host immunity is modulated without suppression. We herein critically examine the synergetic reciprocal relationship between pregnancy and ADs. We review key ADs and their current prognosis and management. Finally, we describe PreImplantation Factor, a peptide secreted by viable embryos that, beyond its essential autotrophic and proimplantation properties, regulates systemic immune response and also proved effective in nonpregnant autoimmune and transplantation models. Hence, PreImplantation Factor may have a key role in improving ADs in pregnancy, and provide a novel drug for treatment of immune disorders in general.