The epidermal growth factor receptor (EGFR) is commonly overexpressed in non-small cell lung cancer (NSCLC). In addition, activating mutations in the EGFR tyrosine kinase domain have been described almost exclusively in NSCLC. Cetuximab, a monoclonal antibody against EGFR, has only modest single-agent activity in advanced NSCLC. A few phase II studies conducted in advanced NSCLC show no significant benefit from adding cetuximab to chemotherapy. However, in vitro observations of synergy between EGFR inhibitors and radiation therapy have been confirmed in the clinical setting of head and neck cancer. The addition of cetuximab to radiotherapy improves survival in patients with locally advanced unresectable squamous cell cancer of the head and neck compared with radiotherapy alone and this combination is being actively studied in locally advanced NSCLC. Research is also ongoing to define the role of cetuximab in combination with other targeted agents. This review will summarize the results of recently published studies on cetuximab and outline current research with this agent in NSCLC.