A significant flow of new data is currently being generated within the field of estrogen receptors and their mechanisms of action. This is primarily a result of the development of estrogen receptor knockout mice and the discovery of the second estrogen receptor, estrogen receptor beta. Both estrogen receptors appear to be involved in a multitude of regulatory events, the details of which will be worked out within the next few years. Estrogen receptor alpha appears to play a major role in the regulation of reproductive events and estrogen receptor alpha knockout female mice are completely infertile. Estrogen receptor beta knockout females have severe but incomplete infertility. Estrogen receptor beta gene mutations may, therefore, be of great clinical interest because they could perhaps explain some cases in which ovarian dysfunction leads to human infertility. Both receptors appear to be of essence for the cardiovascular system. Future studies will determine the relative importance of estrogen receptors alpha and beta in bone, the urogenital tract, the immune system, and the central nervous system, as well as in other estrogen target tissues.