Radiotherapy is a highly effective, targeted therapy for the management of cancer. Technological innovations have enabled the direct integration of imaging technology into the radiation treatment device to increase the precision and accuracy of radiation delivery. As well as addressing a clinical need to better control the placement of the dose within the body, image-guided radiotherapy has enabled innovators in the field to accelerate their exploration of a number of different paradigms of radiation delivery, including toxicity reduction, dose escalation, hypofractionation, voxelization, and adaptation. Although these approaches are already innovative trends in radiation oncology, it is anticipated that they will work synergistically with other innovations in cancer management (including biomarker strategies, novel systemic and local therapies) as part of the broader goal of personalized cancer medicine. This Review discusses the rationale for adopting image-guidance approaches in radiotherapy, and the technology for achieving precision and accuracy in the context of different paradigms within the evolving radiation oncology practice. It also examines exciting advances in radiotherapy technology that suggest a convergence of radiotherapy practice in which patient-specific radiotherapy treatment courses are one of the most personalized forms of intervention in cancer medicine.