Progesterone is an essential hormone in the process of reproduction. It has been extensively studied in the treatment of different gynecological pathologies, as a contraceptive and in assisted reproductive technologies. However, the use of progesterone in the pathophysiology of pregnancy remains controversial. Progesterone, and its synthetic form 17 α-hydroxyprogesterone caproate (17 OHP-C), offer an effective intervention when the continuation of pregnancy is at risk from immunological factors, luteinic and neuroendocrine deficiencies, and myometrial hypercontractility. Progesterone has been successfully used as prophylaxis in the prevention of spontaneous miscarriage, with treatment beginning from the first trimester of pregnancy. There is substantial evidence, too, to indicate that women with idiopathic recurrent miscarriage may benefit from the immunomodulatory properties of progesterone in early pregnancy. The use of progesterone and 17 OHP-C has been extensively studied in the prevention of preterm birth in a variety of settings. Transvaginal ultrasound measurement of cervical length in singleton pregnancies between 19 and 24 weeks' gestation has been deemed the best way to identify women (approximately 2% of the pregnant population) who would benefit from prophylactic progesterone treatment for the prevention of spontaneous preterm birth. This paper reviews the evidence for the safety and efficacy of the use of progesterone in each of these indications.