The selective estrogen-receptor modulators, or SERMs, chemically diverse nonsteroid compounds, have tertiary structures that permit binding to the estrogen receptor. These compounds have either selective agonist or antagonist effects, depending on the target tissue. This article reviews current information concerning the molecular basis of SERM action and the tissue-selective agonist–antagonist effects of this class of medication. The article also offers a perspective on the therapeutic uses of SERMs and compares the SERMs with estrogen and nonestrogen alternatives.