Progesterone, the natural hormone produced by the corpus luteum and other steroid-secreting glands, is endowed with antiestrogenic action and has a fundamental role in the initiation and maintenance of pregnancy and in the regulation of gonadotropin secretion. Although it was discovered half a century ago, it has found little clinical use as a therapeutic agent due to its low potency and extensive degradation following oral administration in comparison with a variety of highly potent synthetic analogs that became available in the last three decades. When delivered systemically, a large proportion of the dose bypasses degradation in the gut and liver, and progesterone can achieve effective levels in target tissues for clinical use. Sustained administration via compressed pellets implanted subdermally or silicone rubber rings placed in the vagina produced circulating levels of progesterone within the lower third of those found in the luteal phase of the human menstrual cycle. Those levels were shown to delay the recovery of fertility in nursing women without adverse effects to the mother or the infant. Progesterone transferred to the babies via the breast milk did not change their rate of pregnandiol-3-alpha glucuronide excretion. It is concluded that sustained administration of the natural hormone progesterone may be an effective and safe contraceptive method for nursing women.