The burden of squamous cell carcinoma of the head and neck (SCCHN) on healthcare systems is expected to rise in line with projected increases in population sizes in general, and the relative proportion of elderly individuals in particular, underlining the need for effective, well tolerated treatment strategies. The epidermal growth factor receptor (EGFR)-targeted IgG1 monoclonal antibody, cetuximab, is the only EGFR-targeted agent currently approved for use in the treatment of SCCHN. Adding cetuximab to standard first-line platinum-based chemotherapy in the treatment of recurrent and/or metastatic SCCHN significantly improved overall survival (hazard ratio [HR] 0.80; P = 0.04), progression-free survival (HR 0.54; P \ 0.001) and response rates (odds ratio 2.33; P \ 0.001), compared to platinum-based chemotherapy alone. This was the first time in 30 years that a significant increase in overall survival had been achieved over platinum-based therapy alone and established cetuximab plus platinum-based chemotherapy as the new standard first-line treatment approach for recurrent and/or metastatic disease. In locally advanced SCCHN, cetuximab plus radiotherapy significantly improved locoregional control (HR 0.68, P = 0.005) and overall survival (HR 0.74; P = 0.03) compared to radiotherapy alone.