Medication-related osteonecrosis of the jaw (MRONJ) is a grievous complication after the long-duration administration of some bone-modifying agents, mainly containing bisphosphonates (BPs), denosumab, angiogenesis inhibitors, immunosuppressors, glucocorticoids, and chemotherapeutics. Its prevalence is rare but mounting due to the widespread application of MRONJ-associated drugs in the aging population and cancer patients. Although MRONJ is excruciating, there has been no specific and efficient remedy for it. To date, the understanding of MRONJ is not thorough, and various theories on MRONJ have been proposed, among which impaired bone remodeling as a result of inhibited osteoclast generation and activity is the predominant one. However, the role of osteocytes in MRONJ has been omitted, given their crucial roles in governing bone metabolism: they not only communicate with osteoblasts for bone formation but also promote osteoclastogenesis.