Introduction: Tumor response and duration of patient survival after treatment with inhibitors of the epidermal growth factor receptor (EGFR) varies considerably between different kinds of EGFR inhibitors, different combination schedules, but also between individual patients. Discussion: Development and introduction of biomarkers into clinical practice is necessary to predict treatment response and thereby to individualize cancer therapy. Due to specific interactions of EGFR inhibitors with biological effects of irradiation, biomarkers are expected to differ for radiation oncology compared to application of the drugs alone or within chemotherapy treatment schedules and therefore need to be established and tested separately. Objectives: The review summarizes the current status of potential predictors for the effect of EGFR inhibitors used as single agents or in combination with chemotherapy. Conclusion: Based on this knowledge and on preclinical radiotherapy data, candidate biomarkers and further research strategies for radiation oncology are discussed.