Radiotherapy remains the foundation of current treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). It has been shown that the addition of concurrent chemotherapy to radiotherapy (chemoradiotherapy, CRT, or chemotherapy-enhanced radiation therapy, CERT) results in improved clinical outcome in terms of both locoregional control and overall survival in some groups of patients. However, CRT is associated with severe, dose-limiting acute toxicities and, in some patients, a higher proportion of late toxicities. In addition, most CRT regimens are platinum-based and there is evidence that the maximum tolerable toxicity has been reached with the dose intensities currently used in bolus cisplatin regimens. Therefore, if we are to further improve outcomes through increased treatment compliance, more effective and more tolerable regimens are needed. Recent results from a phase III randomised study demonstrate that the epidermal growth factor receptor (EGFR) inhibitor cetuximab (Erbituxo) given concomitantly with radiotherapy yields a significant clinical benefit over radiotherapy alone without any increase in radiotherapy-associated toxicity. In this review, we explore the question of the degree to which adding cetuximab improves the efficacy of radiotherapy in locally advanced SCCHN and how the benefits of cetuximab plus radiotherapy compare with those achievable with CRT. (c) 2006 Elsevier Ltd. All rights reserved.