Radiation therapy (RT) is a cornerstone in treating cancer, aiming to eliminate tumor cells while saving surrounding normal tissues. Advances in personalized RT underscore the need for tailored treatment approaches that account for individual patient and tumor-specific factors, maximizing therapeutic efficacy and minimizing side effects. Radiobiology, the basic science of RT, presents crucial insights into cancer and normal tissue responses to irradiation. Central to radiobiology are the seven “Rs,” including DNA Repair, Reoxygenation, Regeneration, Redistribution, Radiosensitivity, immune Reactivation, and Reinforcement by tumor microenvironment, which delineate key determinants of RT outcomes. Understanding these principles not only explains the variability in RT responses but also provides a framework for addressing clinical challenges such as radioresistance. Integrating the “Rs” into personalized RT offers immense potential to refine treatment strategies. The application of these radiobiological principles in combination with advanced imaging, biomarkers, and AI-driven treatment planning is pivotal for optimizing RT outcomes. This chapter highlights the transformative potential of the “Rs” in personalizing RT, bridging the gap between biological understanding and clinical innovation.