Steady-state, circulating progesterone (P4) concentrations are determined primarily by 2 factors: the rate of P4 production, principally by the corpus luteum (CL), and the rate of P4 metabolism, mainly by the liver. Rate of P4 production is primarily related to number of large luteal cells (LLC), differentiation state of LLC, and provision of substrate for P4 production. Steroid production increases 1000-fold from estrus to d 7 with growth of the follicular granulosa cells from 10 mm diameter to 38 mm LLC, a 50-fold increase in cellular volume. The LLC of ruminants are distinguished by a large number of mitochondria and high constitutive P4 production meaning that luteotrophic hormones are not required for P4 production. Nevertheless, cholesterol substrate, primarily in the form of high-density lipoprotein (HDL) is essential for high P4 production by ruminant LLC. Circulating HDL is not limiting in well-fed cattle but may be manipulated by diet. One limiting factor is number of granulosa cells in the follicle and therefore number of LLC. Ovulation of larger follicles or ovulation of multiple follicles can produce greater quantity of luteal tissue and therefore increased luteal P4 production. Regression of the CL is marked by decrease P4 production due to decreased transport of cholesterol to the inner mitochondrial membrane of the LLC. The rate-limiting step in cholesterol transport is StAR protein. Other steroidogenic enzymes remain active as P4 production by the CL plummets. Thus, luteal P4 production can be increased or decreased by hormonal, dietary, and management manipulations. Metabolic clearance rate (MCR) of P4 has been found to vary substantially between cows in different physiological conditions. For example, P4 MCR more than doubles in cows during high milk production as compared with similar size and age nonlactating cows. The P4 metabolism enzymes are concentrated in the liver. Thus, MCR of P4 and other steroids is primarily related to the rate of liver blood flow, which has been related to dry matter intake in dairy cattle. In conclusion, manipulation of P4 production and metabolism appear to be fertile areas for future research aimed at improving fertility in cattle.