Bisphosphonate therapy has been considered standard therapy in the management and care of cancer patients with metastatic bone disease and patients with osteoporosis. The efficacy of these drugs is due to their ability to inhibit osteoclast-mediated bone resorption. However, the postmarketing experience with intravenous and, to a much lesser extent, oral bisphosphonates has raised concerns about potential side effects related to profound bone remodeling inhibition and osteonecrosis isolated to the jaws. We review the risk factors, incidence, pathogenesis, prevention strategies, and management of this new complication.