Pregnancy is an immunological paradox created by the hospitable interaction between the maternal immune system and the allogeneic conceptus in the gravid uterus. The mother is not immunesuppressed during early pregnancy, nor is the conceptus immune-privileged, shielding itself from maternal immune detection by an immunologically inert placenta. Rather, what is becoming clear is that the conceptus and other endocrine mediators, including progesterone, actively shape the maternal immune response during early pregnancy to facilitate growth and development of a functioning placenta. In this regard, conceptual thinking derived from immune cell – pathogen interactions inadequately describe the unique homeorhetic mechanisms mediating early conceptusmaternal interactions. Nonetheless, evidence is mounting that conceptus signals induce a tolerogenic (Th2) bias in immune cell function at the fetal-maternal interface. This is accompanied by tissue remodeling and angiogenesis facilitated by tissue-resident immune cells that sets the trajectory for placental growth and, ultimately, fetal growth. Perturbations in these interactions, including systemic inflammation and various stressors at the earliest stages of pregnancy can interfere with communication between the conceptus and uterus, reducing conception rates and resulting in poor pregnancy outcomes.