A key step forward in the treatment of hormone-dependent diseases has been made since the discovery of tissue-specific steroid receptor modulators (SRMs), or receptor ligands that elicit agonistic or antagonistic effects in a cell- and tissue-dependent manner. In reproductive medicine, selective estrogen receptors modulators (SERMs) and selective progesterone receptors modulator (SPRMs) were discovered and developed since the 1970s. SERMs were first released for the treatment of infertility and later developed in areas such as osteoporosis prevention and breast cancer treatment. The later discovery of SPRMs has provided molecules active on the inhibition of ovulation, on the endometrium and on leiomyoma cells, which are currently being developed for their antiproliferative effects in breast cancer and endometriosis. New molecules and new routes of administration of SERMs and SPRMs are in development for cancer treatment, long-term contraception and endometriosis. Based on the future advancements on the understanding of the mechanisms of action of these compounds, it is to be expected that future SRMs will emerge for newer indications.