Nuclear receptor (NR) superfamily is located in transcriptional regulators class. Due to their important role in controlling many physiological and pathological events, it has become the most important therapeutic targets in clinical trials. Although it is used successfully in many cases allowing the receptor modulating drugs, due to targeted therapy resistance mechanisms of NRs that work for generating new drugs, are still up to date. Most successful target therapy for controlling activity of the receptor, was carried out on the basis of NR signaling pathway. In this review; estrogen receptors (ERs) subtypes, ERs domain structure and general features, ER molecular signaling mechanisms, ER degradation occurring with ubiquitin proteasome pathway, ER degradation triggered by basal and ligand, the effect of estrogen receptor concentration in response to estrogen, ER alpha molecular background of action of agonists and antagonists are explained in detail. The exhaustive information contained in this article is to assist a clearer understanding of receptor function in the control of key points, we believe it would be useful for future therapeutic approaches.Keywords: Nuclear receptors, ER alpha, ER beta, ER degradation.