A significant proportion of pregnancy loss in dairy cows occurs during the first 3 weeks after conception, particularly during the period of conceptus elongation that occurs before implantation. Progesterone (P4) from the corpus luteum plays a major role in regulating endometrial function including conceptus–maternal interaction, pregnancy recognition, and uterine receptivity to implantation. Numerous studies have demonstrated an association between systemic P4 concentrations in the very early stages of pregnancy and likelihood of pregnancy establishment. Low P4 concentrations have been implicated as a causative factor in low pregnancy rates observed in high-producing dairy cows. Elevated concentrations of P4 in the immediate post-conception period have been associated with an advancement of conceptus elongation, an increase in conceptus-derived interferon-tau production and, in some cases, higher pregnancy rates. Elevated P4 advances the transcriptomic changes in the endometrium which normally occur during early pregnancy, resulting in enhanced conceptus elongation; interestingly, the embryo does not have to be present in the uterus during the period of elevated P4 to benefit from it, supporting the concept that the positive effect on conceptus growth is mediated via P4-induced changes in the endometrial transcriptome. Recent studies have demonstrated that the bovine endometrium responds differently to age-matched conceptuses of varying size in both an IFNT-dependent and -independent manner, which may be reflective of the likelihood of successful pregnancy establishment. Multiple strategies have been devised to augment P4 including treatments which provide exogenous P4 (e.g., intravaginal P4 pessaries, P4 injections) or those which enhance the ability of the CL to produce P4 (e.g., administration of human chorionic gonadotrophin). However, despite such effects on conceptus elongation, data on the benefits of post-insemination supplementation with P4 on pregnancy rates are conflicting and, at best, relatively modest. Increased knowledge of the regulation of conceptus-endometrial interactions is necessary to understand and elucidate the causes of pregnancy loss and provide a basis for new strategies to improve pregnancy outcomes and reproductive efficiency.