Endometriosis is a common, benign and chronic gynecological disorder. It is also an estrogen-dependent disorder that can result in intractable dysmenorrhea, heavy and/or irregular periods, painful bowel movements and urination during menstruation and infertility and ultimatively in repeated surgeries. Although surgery to remove endometriotic lesions is effective in relieving endometriosis-associated pain, recurrence rates are high and many women require continuous medical therapy to control symptoms.Endometriosis is a chronic disease of unknown etiology that affects approximately 10% of women in reproductive age. Several evidences show that endometriosis lesions are associated to a hormonal imbalance including estrogen synthesis, metabolism and responsiveness, and progesterone resistance. These hormonal alterations influence the ability of endometrial cells to proliferate, migrate and to infiltrate the mesothelium, causing inflammation, pain and infertility. Hormonal imbalance in endometriosis represents also a target for its treatment. We provide an overview on therapeutic strategies based on innovations of classical hormonal mechanisms involved in the development of endometriosis lesions. The development phase of new molecules targeting these pathways is also discussed. Endometriosis is a chronic disease involving young women and additional biological targets of estrogen and progesterone pharmacological manipulation (brain, bone and cardiovascular tissue) need to be carefully considered in order to improve and overcome current limits of long-term medical management of endometriosis.