In contrast to conventional wisdom, the female immune response is not ‘passive, suppressed, indolent or physically constrained’ when it comes to pregnancy (Medawar, 1953). Instead, immune cells are centrally engaged with all steps of the reproductive process from conception to embryo implantation and placental development. Indeed through an active role in the decision pathway that permits pregnancy progression, the immune system acts in synergy with the reproductive system to ensure healthy reproduction. The biological benefit of a robust immune contribution may be to discriminate between good and bad reproductive opportunities and execute an appropriate response at conception – to sustain and nurture an implanting embryo, or alternatively to actively suppress pregnancy. Emerging information is consistent with this - the immune system has an active function in sensing and evaluating parameters of male gamete quality and embryo viability, as well as markers associated with seminal fluid and the embryo that are relevant to embryo-maternal compatibility. This is mediated by immune contributions to pre-implantation embryo development, progesterone synthesis, and endometrial receptivity. Since the immune response is modulated by a woman’s infectious, inflammatory, stress, nutritional and metabolic status, immune influence on progression or disruption of pregnancy may be further influenced by environmental stressors and resource availability. From an evolutionary perspective, such a ‘quality control’ function ensures appropriate investment of limited female resources and opportunities for reproduction.  Pathologies such as implantation failure or recurrent miscarriage may be due to over-zealous quality control, or an indecisive commitment to tolerance or rejection. The challenge now is to define the critical cytokines and seminal fluid signals that influence this nexus - some factors are paternal, some maternal, and some may be specific to the partnership. Understanding immune decision-making at conception will offer new ways to promote fertility and will shed light on infertility disorders with an immune aetiology.