Objective: To review the use of progesterone in the prevention of postnatal depression and to present a case report. Clinical Features: A 36-year-old lady with a history of severe postnatal depression following two previous deliveries was treated with prophylactic progesterone after the birth of her third child. She received intramuscular progesterone injections for one week and was then commenced on progesterone suppositories. Therapy was continued for three months. She developed no symptoms of postnatal depression and no side effects were apparent.