Endometriosis is one of the most frequent benign gynecological diseases that affect women. Little is known about the pathogenesis and etiology of endometriosis, despite the numerous studies performed in this field. Although endometriosis is a benign disease, the endometrial tissue, after attachment to the peritoneum, has the ability to grow and invade the surrounding tissues. Similar to neoplastic growth, local extracellular proteolysis might take place, and therefore, the fibrinolytic system may be involved. An altered expression of several components of the fibrinolytic system in the endometrium and peritoneal fluid of women with the disease has been suggested as a key factor in the establishment of the endometriotic lesions. There is evidence of increased fibrinolytic activity in the eutopic endometrium of these women, resulting in endometrial fragments with a high potential to degrade the extracellular matrix and facilitate implantation. The peritoneum possesses an inherent fibrinolytic activity that is responsible for the degradation of the fibrin deposits originated after an injury. This physiological function allows a correct repair of the mesothelium, and therefore, prevents the formation of adhesions. Peritoneal fluid of women with endometriosis and pelvic adhesions has shown to have an increased fibrinolytic activity that may be implicated in reducing the formation of new adhesions. Endometriotic tissue has abnormal proteolytic capacity, which is determined by modifications of the fibrinolytic parameters in this tissue. Proteolytic status is determined by the imbalance between plasminogen activators and plasminogen activator inhibitors, which are expressed differently depending on the type of lesion considered and the stage of the disease. The aim of the present study is to review the role of the plasminogen activator system in endometriosis, consider the clinical implications and focus on possible further research efforts and therapeutic applications in this disease.