Bisphosphonates (BPs), in the past erroneously referred to as diphosphonates, were first synthesized in Germany, in 1865. BPs are stable analogs of pyrophosphate that are naturally occurring modulators of bone metabolism and have been synthesized and used since the 19th century; However, their in-vitro ability to inhibit the precipitation of calcium phosphate was applied clinically in the 1960s. Since then, the main clinical application was in the treatment of certain resorptive bone diseases (osteoporosis, Paget’s disease, and hypercalcemia associated with certain malignancies such as multiple myeloma and bone metastasis from the breast or prostate). Later on, in 2002, the Food and Drug Administration reviewed some cases of osteonecrosis of the jaw in cancer patients who had undergone BP therapy. In 2003, Marx introduced this clinical condition in the medical literature. BP-induced osteonecrosis of the jaw is related to the development of avascular necrosis or dead jaw bones and cannot easily be treated with conventional medical and/or surgical intervention. Because of the poor treatment outcomes, many studies focused on its preventive measures. In this study, we review the different risk factors and associated preventive measures against BRONJ.