Progesterone is a progestin that occurs naturally. It is produced in the body by the ovaries, testes, placenta, and adrenal cortex. Progesterone is generally used to treat amenorrhea and irregular uterine bleeding, as well as as a contraceptive. Progesterone is also used to avoid early pregnancy failure in women with corpus luteum insufficiency, including those who utilize assisted reproductive technology (ART). Furthermore, the use of progesterone for preterm delivery prevention is being researched. Preliminary studies suggest that progesterone may be useful in preventing preterm birth in high-risk women, particularly those with a history of preterm birth;1 however, the ideal dosage and route have yet to be discovered. If progesterone is to be used to prevent preterm birth, the American College of Obstetricians and Gynecologists (ACOG) Committee recommends that it be used only in women who have a history of spontaneous birth at 37 weeks gestation, until more data supporting its use in other high-risk women becomes available. 2 A study has been published that supports the use of vaginal progesterone in women with a short cervix. 3 Progesterone is commercially available as an intramuscular injection, intravaginal gel, intravaginal insert, oral capsules, or powder for use in impromptu formulations (e.g., vaginal suppositories). A yearly progesterone-releasing IUD (Progestasert®) insertion has been discontinued. The FDA authorized progesterone in 1939. Micronized progesterone capsules for oral administration were approved for secondary amenorrhea in May 1998, and for the prevention of endometrial hyperplasia in postmenopausal women with an intact uterus receiving estrogen replacement treatment in December 1998. A progesterone vaginal gel (Crinone®) was licensed in May 1997 for progesterone supplementation or replacement as part of an ART regimen for infertile women; a second intravaginal gel, ProchieveTM, was released to the US market in 2002. Endometrin®, a vaginal insert for progesterone supplementation as part of an ART therapy in infertile women, was approved in June 2007.