The discovery of ER beta in the middle of the 1990s represents a paradigm shift in our understanding of estrogen signaling. It has turned out that estrogen action is not mediated by one receptor, ER alpha, but by two balancing factors, ER alpha and ER beta, which are often antagonistic to one another. Excitingly, ER beta has been shown to be widespread in the body and to be involved in a multitude of physiological and pathophysiological events. This has led to a strong interest of the pharmaceutical industry to target ER beta by drugs against various diseases. In this review, focus is on the role of ER beta in malignant diseases where the anti proliferative activity of ER beta gives hope of new therapeutic approaches. (C) 2010 Elsevier Inc. All rights reserved.