The corpus luteum (CL) releases progesterone, which acts on the endometrium to induce release of histotroph that supports the free-floating conceptus and prepares for epithelial-chorial placentation. Two steroidogenic cell types, which are classified based on size, contribute to serum progesterone concentrations. Large luteal cells produce the bulk of progesterone because of constitutively active protein kinase A. Small luteal cells also contribute to serum progesterone concentrations through release of progesterone in response to luteotrophic stimuli. The CL is maintained in ruminants until endometrial-derived prostaglandin F2 alpha (PGF) initiates functional and structural regression. The decline in serum progesterone and loss of negative feedback on the hypothalamus and anterior pituitary sets up hormonal responses resulting in a new estrous cycle that is characterized by estrus, ovulation and formation of a new CL. If a conceptus is present, interferon tau (IFNT) is released from the conceptus, which binds receptors in the endometrium and prevents up-regulation of estrogen receptor (ESR1) and consequently oxytocin (OXT) receptor (OXTR). As a consequence, pulses of PGF are disrupted which results in rescue of the CL from luteolysis. In addition to these paracrine actions, early pregnancy also has direct endocrine action on the CL through inducing IFNstimulated genes (ISGs) in the CL and resistance of the CL to PGF. Endocrine actions of IFNT have been described through detection of IFNT in uterine vein blood, induction of several ISGs in the CL during pregnancy, and following both in vivo (via miniosmotic pumps) and in vitro (in cultured small, large, and mixed luteal cells) delivery of recombinant ovine (ro) IFNT. These endocrine actions of IFNT might be applied to reducing embryo mortality and associated economic consequences in ruminants.