Nineteen years have passed since our previous review in this journal in 1999 regarding estrogen receptors. At that time, we described the current assessments of the physiological activities of estrogen and estrogen receptors. Since that time there has been an explosion of progress in our understanding of details of estrogen receptor–mediated processes from the molecular and cellular level to the whole organism. In this review we discuss the basic understanding of estrogen signaling and then elaborate on the progress and current understanding of estrogen receptor actions that have developed using new models and continuing clinical studies.