Background: Numerous studies have demonstrated that Leukemia Inhibitory factor (LIF) plays an essential role in embryonic implantation. Vaginal application of pegylated LIF antagonists can successfully prevent implantation and pregnancy in mice. The development of non-hormonal, female-controlled contraceptives is imperative, as combined oral contraceptives are associated with depression and are not feasible for use in all women.Methods: This paper reviews 44 studies regarding LIF, implantation, hormonal contraceptives and the use of LIF antagonists as a means to inhibit pregnancy.Summary: Current research indicates that LIF-modulation could be effective as a non-hormonal contraceptive method, although researchers should be wary of the negative side effects associated with systemic LIF modulation. Vaginal application of LIF antagonists could decrease the risk of negative side effects.