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Medication-related osteonecrosis of the jaw (MRONJ), an adverse reaction to medication, has been reported since 2002, at first in cancer patients with bone metastases treated intravenously with pamidronate or zoledronate, and later in patients taking oral bisphosphonate for the treatment of osteoporosis. Several cases of MRONJ have also been described in patients treated with antiangiogenic drugs with a so-called biological target (bevacizumab, sunitinib, sorafenib). Oxygen/ozone therapy for MRONJ treatment represents a possible and efficient alternative to the two main therapeutic approaches currently in use, antibiotic therapy and surgery. Since 2010, I have diagnosed 51 MRONJ cases at ASST Fatebenefratelli-Sacco. Subsequently and following the approval of the Ethics Committee (2015), patients with MRONJ level 1 and 2 have been included in an experimental protocol with oxygen/ozone therapy: Treatment of bisphosphonate-related osteonecrosis of the jaw with oxygen/ozone therapy and surgical debridement with piezoelectric scalpel. The study is currently running and up to now six out of fourteen patients healed perfectly. Among these six, four spontaneously or almost spontaneously have expelled the necrotic part without undergoing surgery. In three cases, there was only an improvement in symptoms. Five patients are currently being treated. Because of its antiseptic properties, oxygen ozone therapy reduced the effects of infection and inflammation, while the bio stimulant action of this therapy promoted the demarcation of bone sequestration and soft tissue healing.