This chapter will discuss the effectiveness of predictive biomarkers in predicting the risk of mandibular osteoradionecrosis (ORN) in patients with head and neck cancers (HNC) who undergo radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Furthermore, it will explore the role of these biomarkers in the pathogenesis of ORN. Blood-borne biomarkers, such as neutrophils, monocytes, lymphocytes, platelets, hemoglobin (Hb), and albumin, before RT or CCRT have the potential to predict an increased risk of ORN following treatment. Various aspects of ORN pathogenesis, such as hypoxia, vascular thrombosis, inflammation, and fibrosis, have been linked to these biological indicators. Specific biomarkers such as hemoglobin (Hb), hemoglobin-to-platelet ratio (HPR), pan-immune-inflammation value (PIV), and host index (H-index) have been proven effective in predicting the incidence of ORN. While the exact functions of cytokines and chemokines are not yet established, they are believed to play critical roles in the development of ORN. Predictive biomarkers have the potential to accurately forecast the risk of ORN in patients with HNC who are undergoing RT or CCRT. Hence, they can help categorize patients according to their risk level and implement better preventive measures.