This manuscript reviews the effect of progesterone (P4) during timed AI protocols in lactating dairy cows. Circulating P4 is determined by a balance between P4 production, primarily by the corpus luteum (CL), and P4 metabolism, primarily by the liver. In dairy cattle, the volume of luteal tissue is a primary determinant of P4 production; however, inadequate circulating P4 is generally due to high P4 metabolism resulting from extremely elevated liver blood flow. Three sections in this manuscript summarise the role of P4 concentrations before breeding, near the time of breeding and after breeding. During timed AI protocols, elevations in P4 are generally achieved by ovulation, resulting in an accessory CL, or by supplementation with exogenous P4. Elevating P4 before timed AI has been found to decrease double ovulation and increase fertility to the timed AI. Slight elevations in circulating P4 can dramatically reduce fertility, with inadequate luteolysis to the prostaglandin F2α treatment before timed AI being the underlying cause of this problem. After AI, circulating P4 is critical for embryo growth, and for establishment and maintenance of pregnancy. Many studies have attempted to improve fertility by elevating P4 after timed AI with marginal elevations in fertility. Thus, previous research has provided substantial insights into mechanisms regulating circulating P4 concentrations and actions. Understanding this prior research can focus future research on P4 manipulation to improve timed AI protocols.