A large majority of pregnancy loss in cattle occurs during the first three weeks after conception, particularly during the peri-implantation period. This review integrates established and new information on the biological role of ovarian progesterone (P4), prostaglandins (PGs) and interferon tau (IFNT) in endometrial function and conceptus elongation during the peri-implantation period of pregnancy in ruminants. Progesterone is secreted by the ovarian corpus luteum (CL) and is the unequivocal hormone of pregnancy. Prostaglandins are produced from both the endometrium as well as conceptus trophectoderm during early pregnancy. Interferon tau is produced solely by the conceptus trophectoderm and is the maternal recognition of pregnancy signal that inhibits production of luteolytic pulses of PGF2α by the endometrium to maintain the CL and thus production of P4. Conceptus-endometrial interactions in ruminants are complex and involve carefully orchestrated temporal and spatial alterations in endometrial gene expression during pregnancy. Available results support the idea that the individual, interactive, and coordinated actions of P4, PGs, and IFNT regulate uterine receptivity to conceptus implantation by controlling expression of genes in the endometrium and that their actions are essential for conceptus elongation. One outcome of gene expression changes in the endometrial epithelia is alterations in lumenal secretions that govern conceptus elongation via effects on the trophectoderm. An increased knowledge of conceptusendometrial interactions during early pregnancy in ruminants is necessary to understand and elucidate the causes of infertility and recurrent pregnancy loss and to provide a basis for new strategies to improve fertility, pregnancy outcomes and thus reproductive efficiency.