Introduction: Endometriosis, histologically defined as the presence of endometrium-like tissue - glands and stroma - that develops outside of the uterine cavity, is still an enigmatic disease responsible for pelvic pain and infertility. The current treatments of endometriosis are surgery and hormonal therapies that act by suppressing ovulation and/or directly on steroid receptors located in endometriotic lesions. Areas covered: New hormonal and non-hormonal therapies are being developed for the treatment of endometriosis-related pain. The authors review the state of advancement and the results of novel treatments studied in registered trials ( www.ClinicalTrials.gov ). Cellular signaling pathways activated in endometriotic cells, which constitute potential targets for future treatments, are also described. Expert opinion: Therapeutic research efforts should focus on identifying and testing substances capable of acting locally on the lesions themselves, without interfering with ovulation, in order to be efficacious on both pain symptoms and infertility.