Whereas the essential role of progesterone in the maintenance of pregnancy is accepted generally, the mechanisms that suppress progesterone’s function near term to allow labor and delivery of the conceptus are still shrouded in uncertainty. In most subprimate placental mammals, the withdrawal of progesterone before the initiation of labor is manifest by a significant drop in circulating progesterone levels, which is due to either luteolysis or changes in placental steroidogenesis, which shunts precursors towards estrogen production. No such events can be demonstrated in human pregnancy. In this review, we shall present a brief historic background of the research that led to the concepts of “progesterone block” and its withdrawal, based on experiments with rabbits and laboratory rodents, and discuss some of the more recent ideas about “functional progesterone withdrawal,” in an attempt to bridge the apparent differences between the regulation of parturition in human and subprimate mammals.