Retention of fetal membranes (RFM), where the fetal placenta is not expelled within 8-12 hr after calving, lowers bovine productivity and fertility, resulting in significant economic loss to the dairy industry. Several risk factors that predispose an individual to RFM are known, but a unifying pathogenesis remains elusive due to its multifactorial etiology. Fetal membrane separation and expulsion after parturition involves structural and immunological changes of the bovine placentome that are governed predominantly by steroid hormones and the prostaglandin milieu of late pregnancy and parturition. Maturation of the placentome, a gradual and concerted event of late gestation, is likely initiated by the up-regulation of fetal major histocompatibility complex class I in the interplacentomal region-which increases the apoptosis of binucleate and other trophoblastic cells, the degradation of collagen in the extracellular matrix by matrix metalloproteinases, and an influx of phagocytic leukocytes. Shear force further distorts the crypt architecture of the mature placentomes when they are forced against the fetus during the second stage of labor. Cotyledon dehiscence from the caruncular crypts is completed following fetal expulsion as a result of acute shrinkage of the cotelydonary villi as well as reduced perfusion to the caruncle; the secundinae is expelled by uterine contractions. A better understanding of placentomal maturation, intra-partum, and immediate postpartum changes of the placentome should help develop strategies for the treatment and prevention of RFM. The present review proposes a model of placentome maturation and separation of fetal membranes in the dairy cow.