Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but severe, complication of applying inhibitors of osteoclasts, specifically bisphosphonates and the monoclonal antibody of receptor activator of nuclear factor kappa-Β ligand (RANKL), inhibitors of angiogenesis, and some chemotherapeutics. MRONJ is painful for the patients, while current treatments are unsatisfactory. Thus, it is imperative to understand the etiology and pathogenesis of MRONJ to improve treatment options and enable prevention. Various hypotheses have been proposed over the years to elucidate the pathogenesis of MRONJ. Noticeably, impaired osteoclastogenesis shines some light on novel preventive and treatment strategies. In this review, we summarized the current understanding of the role of osteoclastogenesis in the development of MRONJ and have put forward a hypothesis concerning the application of BMP2 in the clinical management strategy for MRONJ.