The recent publication of 2 large randomized trials of 17 alpha hydroxyprogesterone caproate (17P) and progesterone suppositories, respectively, for the prevention of premature labor have renewed interest in the use of progesterone to prevent preterm birth. The results of these trials have reinforced the positive results of earlier smaller trials of 17P to prevent preterm delivery. A large body of evidence attests to the lack of teratogenic effects of 17P in pregnancy. Although progesterone is known to have many actions beneficial to the maintenance of pregnancy, the exact mode of action of 17P therapy in preventing preterm labor and delivery is not known. Current evidence supports the use of 17P treatment, begun early in the second trimester of gestation and continued weekly until 36 weeks, for women with a history of a previous spontaneous preterm delivery. At present no evidence exists for the use of 17P to prevent preterm delivery in women with multiple gestation, a short uterine cervix, or other high-risk conditions. The use of 17P or other progestins should not be encouraged for these indications outside of randomized trials. At present no evidence exists for the efficacy of any oral progesterone compound in preventing preterm labor. Four trials reporting the use of a progestational drug in patients with symptoms of preterm labor found no efficacy in prolonging pregnancy, and the use of 17P or other progestational drugs as tocolytic therapy should not be encouraged.