Bisphosphonate-related osteonecrosis of the jaws represents a widely studied pathology. Moreover, some cases of ONJ related to the use of Denosumab have also been described recently. Denosumab is a human monoclonal antibody. It is bound with high affinity and specificity to nuclear factor kappa beta activating factor ligand (RANKL) and prevents Rank activation with reduction bone reabsorption. However, medium and long term effects of this drug are not unknown yet. The main goal of the present report is twofold. First, we point out the serious complications that these drugs might provoke. Second, we describe four cases of Denosumab related ONJ in order to expand the knowledge about the proper management of this rare complication.