High epidermal growth factor receptor (EGFR) expression is a feature of human tumours and is an adverse prognostic factor for radiotherapy outcome. High expression is associated with benefit from accelerated radiotherapy in patients with head and neck squamous cell carcinoma. Anti-EGFR strategies potentiate the effects of radiotherapy and the inhibition of deoxyribonucleic acid repair appears to be important amongst a wide range of mechanisms, which include effects on angiogenesis, differentiation and the immunological response. There is considerable interest in exploring combined modality therapies involving radiation and EGFR antagonists for the curative treatment of cancer patients. Important issues in designing new trials are to investigate optimal scheduling and to establish biobanks to develop biomarkers for future patient selection. © 2008 The British Institute of Radiology.