Bisphosphonates (BP) are the current standard of care for preventing malignant skeletal related-events. Recent reports have documented the relationship between osteonecrosis of the jaws (ONJ) and the use of BPs. Based on the opinion of experts, the purpose of our analysis was to summarize current knowledge, to propose therapeutic options, and to define areas of research. Identified risk factors were long-lasting exposure to BPs, intravenous nitrogen-containing BPs, and poor dental status. Three major hypotheses could explain the genesis of ONJ: excess of bone turnover inhibition, antiangiogenic effect, and local infection. Before the onset of therapy, the dental status must be controlled, and followed during treatment. Dental procedures could worsen the risk of ONJ, and indications must be well evaluated. When an ONJ occurs, the management should be adapted according to its extent. Thereby, a customization of BP therapy should be applied taking into account the aggressiveness of the underlying disease.