Radiotherapy is one of the main treatments for solid tumors. The total dose that can be delivered to the tumor is limited by the radiation amount received by the surrounding normal tissues, which are at risk of developing acute and late radiation-induced effects. Areas covered: Severe late radiation-induced toxicity occurs in 5% to 10% of patients following radiotherapy. However, the current radiotherapy and radiation protection protocols do not take into account the variations in radiosensitivity among individuals. This review will focus on late radiotherapy-induced side effects and on the different cellular assays (γ-H2AX/53BP1 focus formation, G2 metaphase, G0 micronucleus formation and radio-induced apoptosis in CD8(+) T-lymphocytes: level I evidence) that have been developed to predict their occurrence in patients. Expert commentary: The routine prediction of late radiation-induced toxicity in normal tissues in the clinic will allow personalized radiotherapy with better outcome and less side effects. Patients at low risk of late toxicity could receive a higher total dose to the tumor. Conversely, patients at high risk of late toxicity should receive lower radiation doses per fraction, using state-of-the-art treatment techniques, or alternative therapies to avoid radiation-induced side effects.