Despite the widespread use of bisphosphonates and their unequivocal efficacy for the treatment of various disease states, osteonecrosis of the jaw remains one of the most feared complications associated with their use. Current evidence, however, suggests that there is also a relationship between occurrence of osteonecrosis of the jaw and use of other classes of pharmacotherapies namely RANKL inhibitors as well as angiogenesis inhibitors. Although these drugs have different mechanisms of action than bisphosphonates, they all seem to interfere with the bone remodeling process i.e. alter the balance between bone resorption and bone formation which may be the most plausible explanation for pathogenesis of osteonecrosis of the jaw. The main objective of this review is to introduce the readership to a number of relatively new medications that may cause osteonecrosis of the jaw. Accordingly, we will summarize latest findings from clinical studies, meta analyses and case reports published in medical literature on this topic. For some of these medications, the evidence may not appear as robust as that for bisphosphonates; yet, the possibility of this adverse event occurring with these non bisphosphonate drugs should never be precluded unless proven otherwise. Thus, it is imperative that health care providers implement preventive measures so as to circumvent the incidence of osteonecrosis of the jaw. In this day of age where medical care is becoming personalized, we will highlight some of significant findings from studies seeking to identify genetic markers that may potentially play a role in development of osteonecrosis of the jaw.