Progesterone is an essential hormone in the process of reproduction. It is involved in the menstrual cycle, implantation and is essential for pregnancy maintenance. Although the pharmacokinetics and pharmacodynamics of progesterone have been well studied, and since 1935 it has been synthesised and is now available commercially, its use in the pathophysiology of pregnancy remains controversial. One of these concerns is the way in which the hormone is administered, with parenteral use proving the best way to obtain optimal plasma levels. Another concern is the paucity of randomised controlled trials and the different dosages and populations studied. As a result, the therapeutic application of progesterone in pregnancy is restricted to the prevention and treatment of threatened miscarriage, recurrent miscarriage and preterm birth. Progesterone is efficacious when continuation of pregnancy is hampered by immunological factors, luteinic and neuroendocrine deficiencies and myometrial hypercontractility. This may explain the reduction in the incidence of preterm birth in high risk pregnant women using high-dosage prophylactic progesterone.