In contrast to conventional wisdom and Medawar’s instrumental hypotheses [1], the female immune response is not ‘passive, suppressed, indolent or physically constrained’ in pregnancy. Instead, immune cells are activated and aware of fetal antigens, and indeed centrally engaged in all steps of the reproductive process from conception to embryo implantation and birth. We have demonstrated that the phenotype and strength of the T cell response to paternally-derived alloantigens at conception is responsive to cytokines and miRNAs present in and controlled by male partner seminal fluid, maternal hormones and signalling factors released by the embryo [2]. The maternal response to seminal fluid in turn contributes to either facilitating or blocking pre-implantation embryo development, progesterone synthesis, endometrial receptivity and placental morphogenesis. Immune determinants of progression or disruption of pregnancy may be further influenced by the female’s exposure to environmental stressors and resource availability. The biological benefit of a robust immune response at the outset of pregnancy may be to discriminate between good and poor reproductive opportunities and execute an appropriate response – to sustain and nurture an implanting embryo through generating robust T cell tolerance, or alternatively to actively suppress pregnancy through inflammatory mediators and fetal antigen-specific effector cells. From an evolutionary perspective, such a ‘quality control’ function would ensure appropriate investment of limited female resources and reproductive opportunities.  Reproductive disorders may arise when quality control is over-zealous, or indecisive. Determinants of this nexus are likely to include paternal, maternal and fetal factors, and may be influenced by partner compatibility. Understanding immune regulation of reproductive quality control will offer new ways to consider fertility and infertility and the tension between maternal, paternal and fetal interests.