Estrogen has important physiological effects on the growth and function of hormone-dependent tissues, and the link between estrogen and breast cancer has been deciphered at the end of the 20th century. Tamoxifen, one of the first generation selective estrogen receptor modulators (SERMs), has been the gold standard of first-line therapeutic drugs for all stages of estrogen-dependent breast cancer and has been found to reduce the incidence of breast cancer in high-risk pre- and postmenopausal women. Raloxifene, a second-generation SERM, was recently approved by FDA to decrease the risk of invasive breast cancer in postmenopausal women. During these years, many other novel types of SERAMs are being studied. This review highlights their recent advances. The discovery of selective estrogen receptor alpha modulators (SERAMs) and the latest information about their clinical and preclinical trials will be introduced intensively.