This review integrates established and new information on the role of progesterone in uterine biology of ruminants. Establishment of pregnancy in ruminants occurs during the peri-implantation period and involves growth of the blastocyst, elongation of the conceptus (embryo and extraembryonic membranes), and suppression of the endometrial luteolytic mechanism to maintain progesterone production by the ovary. Conceptus elongation involves exponential increases in length and weight of the trophectoderm and onset of extraembryonic membrane differentiation, including gastrulation of the embryo and formation of the yolk sac and allantois that are vital for embryonic survival and formation of a functional placenta. Antiluteolytic effects of the elongating conceptus are due to production of interferon tau (IFNT) by the trophoblast that has a paracrine effect to inhibit upregulation of oxytocin receptors in the endometrial epithelia, thereby disrupting uterine release of luteolytic prostaglandin F_2α (PGF) pulses. Survival of the blastocyst and elongation of the conceptus requires embryotrophic factors (ions, amino acids, carbohydrates, proteins, lipids, and other substances) from the epithelia of the uterus, and those embryotrophic factors are primarily regulated by progesterone. Available results from studies in sheep support the idea that the individual, interactive, and coordinated actions of progesterone, IFNT, prostaglandins, and cortisol regulate expression of elongation- and implantation-related genes in the endometrial epithelia and are essential regulators of conceptus elongation. The outcome of these gene expression changes is alterations in endometrial epithelial secretions that govern conceptus elongation. Elevated concentrations of circulating progesterone immediately after conception have been associated with an advancement of conceptus elongation, an increase in IFNT production and, in some studies, higher pregnancy rates in cattle. An increased knowledge of progesterone biology and conceptus-endometrial interactions is necessary to understand and elucidate the causes of recurrent pregnancy loss and to provide a basis for new strategies to improve pregnancy outcome and reproductive efficiency in ruminants.