Despite the extensive research, endometriosis remains an enigmatic disease as up to now there is no consensus regarding the exact underlying mechanisms which could explain its development and progress. A local environment enriched in estrogens, progesterone resistance, local inflammatory response and multiple other molecular alterations appear to be pivotal events in the establishment and development of ectopic tissue. In the light of the evidence produced by molecular pathology research, in vivo and in vitro studies, modifications in current treatment options are anticipated. Current management of endometriosis is based on pharmacologic treatment and surgical intervention. In particular, combined oral contraceptives, danazol, gonadotropin-releasing hormone (GnRH) analogues and progestins have been extensively used in clinical practice. Novel agents that will hopefully improve the therapeutic potential include aromatase inhibitors, immunomodulators, anti-inflammatory agents, steroids receptor modulators and GnRH antagonists. It is still early for enthusiasm as there is limited knowledge about their short- and long-term side effects, their optimal administration route, their selectivity towards their target genes and the duration of treatment. Although there is a continual report of novel findings, the application of them in clinical practice is a long-lasting procedure requiring longitudinal clinical trials so as to achieve a balance between efficacy and safety.