Sir George Beatson proposed a connection between breast cancer and ovary more than a century ago. It took several decades to the discovery of hormone estrogen and a few more decades when Elwood Jensen announced the discovery of estrogen receptor. His work led to our understanding of how hormones control target gene transcription via their receptors. Several laboratories made major contributions toward our understanding of hormone action. To date, 49 nuclear hormone receptors have been identified that form the nuclear receptor family and carry out a myriad of metabolic functions. Most notably, they are targets for therapy. Jensen and colleagues made ER antibodies that were used to develop ER assay kits in breast cancer specimens. ER contents in breast cancer patients proved to be useful in deciding mode of treatment. Soon after the discovery of ER, the antiestrogen, tamoxifen, which was originally developed as a female contraceptive, was repurposed for breast cancer management, and later it was used as a prophylactic in those women who were in high risk for breast cancer.