Technological advances and clinical research over the past few decades have given radiation oncologists the capability to personalize treatments for accurate delivery of radiation dose based on clinical parameters and anatomical information. Eradication of gross and microscopic tumours with preservation of health-related quality of life can be achieved in many patients. Two major strategies, acting synergistically, will enable further widening of the therapeutic window of radiation oncology in the era of precision medicine: technology-driven improvement of treatment conformity, including advanced image guidance and particle therapy, and novel biological concepts for personalized treatment, including biomarker-guided prescription, combined treatment modalities and adaptation of treatment during its course.