Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. Thesequence similarities of human ERα, mouse ERα, rat ERα, dog ERα, and cat ERα are above 90%, but structuresof ERα may different among species. Estrogen can be agonist and antagonist depending on its target organs. Thishormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity(RBA) of ER and estrogen species in comparison to 17β-estradiol (E2), which is a natural ligand of both ERαand ERβ. The RBA of the estrogen species are as following: diethyl stilbestrol (DES) > hexestrol > dienestrol> 17β-estradiol (E2) > 17- estradiol > moxestrol > estriol (E3) >4-OH estradiol > estrone-3-sulfate. Estrogenmimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ERpositive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have becomeeffective tools for modern drug discovery. These provide three dimensional structures of many transmembranereceptors and enzymes, which are important targets of de novo drug development. The estimated inhibitionconstants (Ki) from computational model have been used as a screening procedure before in vitro and in vivostudies.