Cancer is a dynamic disease that will affect about 40% of the population during their lifetime. Tumor cells typically become more heterogeneous over time resulting in a mixed population of cells with distinct morphological and phenotypic profiles and molecular signatures as well as varying degrees of sensitivity to treatment. Radiotherapy (RT) is used in treating nearly 50% of all cancer patients. However, recurrence will still occur in some patients post-RT, with or without metastasis resulting in poor survival. This could be due to residual disease or the selection of pre-existing intrinsic or evolved radiation resistant cells. Personalized cancer therapy aims to tailor RT based on the unique sensitivity and biology of the patients’ tumor. To achieve this, a means of accurately characterizing radiosensitivity is necessary. Biomarkers of radiation sensitivity can be used to adjust the treatment plan to the sensitivity of the patient and that of their tumor leading to a more optimal therapeutic outcome. Therefore, the identification of biomarkers of radiation sensitivity which can be applied to maximize tumour control, while minimizing radiation toxicity holds the potential to yield high clinical benefits.