PIP: Contraceptive techniques that selectively impair endometrium receptivity have the potential to reduce the risk of cardiovascular complications associated with hormonal methods. However, further research is needed to provide better treatment when oral estrogen is contraindicated, to improve tolerance of progestin-only contraceptives, and identify alternative techniques that will not interfere with the endocrine events of the cycle. This article presents an overview of the endometrial approach to contraception. Discussed are endometrium physiology and the mechanisms of hormonal contraception, endometrial modifications following hormonal contraceptive use, emergency contraception, and intrauterine steroid administration. Outstanding research issues include the mechanisms of endometrial bleeding, definition of molecular and cellular targets for an endometrial approach to contraception, progesterone action, integrins, placental protein 14, insulin growth factor binding protein-1, and plasminogen activators. Short-term developments in this area are expected to include the intrauterine administration of steroids and continuous administration of antiprogestins at doses that do not interfere with secretion. Long-term development will focus on defining new targets for a pharmacological approach in a tissue-specific manner.