Deep infiltrating endometriosis (DIE) is the most aggressive of the three phenotypes that constitute endometriosis. It can affect the whole pelvis, subverting the anatomy and functionality of vital organs, with an important negative impact on the patient’s quality of life. The diagnosis of DIE is based on clinical and physical examination, instrumen-tal examination, and, if surgery is needed, the identification and biopsy of lesions. The choice of the best therapeutic approach for women with DIE is often challenging. Therapeutic options include medical and surgical treatment, and the decision should be dictated by the patient’s medical history, disease stage, symptom severity, and personal choice. Medical therapy can control the symptoms and stop the development of pathology, keeping in mind the side effects derived from a long-term treatment and the risk of recurrence once suspended. Surgical treatment should be proposed only when it is strictly necessary (failed hormone therapy, contraindications to hormone treatment, severity of symp-toms, infertility), preferring, whenever possible, a conservative approach performed by a multidisciplinary team. All therapeutic possibilities have to be explained by the physicians in order to help the patients to make the right choice and minimize the impact of the disease on their lives.