Radiation-induced xerostomia (RIX) is a common and debilitating side effect of head and neck cancer radiotherapy, significantly impacting patients' quality of life. This review comprehensively summarizes the current understanding of RIX, encompassing its clinical quantification, underlying pathophysiology, and established and emerging treatment modalities. We explore various objective and subjective measures used to quantify salivary flow and assess the severity of xerostomia in clinical settings. The pathophysiological mechanisms leading to RIX are elucidated, including radiation damage to salivary glands, alterations in saliva composition, and the role of inflammatory processes. Current treatment strategies, such as saliva substitutes and stimulants, are discussed alongside their limitations. Furthermore, we delve into novel investigational approaches, including gene therapy, stem cell transplantation, and pharmacologic interventions, offering promising avenues for future RIX management. This review provides clinicians and researchers with a comprehensive overview of RIX, highlighting the need for continued research to develop more effective preventative and therapeutic strategies to alleviate this burdensome condition. Semin Radiat Oncol 35:278-284 (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.