Inhibition of the epidermal growth factor receptor (EGFR) pathway has emerged as a proven strategy for the treatment of advanced-stage non-small-cell lung cancer (NSCLC). Cetuximab is a chimeric monoclonal antibody that inhibits EGFR by binding to the extracellular domain of the receptor. The relatively modest anticancer activity as monotherapy in NSCLC has prompted the evaluation of cetuximab as part of novel combination regimens. The safety of cetuximab in combination with the commonly used platinum-based 2-drug regimens in NSCLC has been established in several phase II studies. Recently, the addition of cetuximab to the regimen of cisplatin and vinorelbine resulted in improved overall survival in patients with advanced NSCLC with EGFR-expressing tumors. In contrast, a study in unselected advanced NSCLC patients failed to demonstrate a statistically significant improvement in overall survival with cetuximab in combination with a carboplatin and taxane regimen. It is hoped that identification of predictive biomarkers would lead to the optimal utilization of cetuximab in combination with chemotherapy. The combination of cetuximab with radiotherapy for patients with locally advanced NSCLC has demonstrated promising results in a phase II study and is now being evaluated in a confirmatory trial. This article reviews the clinical data with cetuximab in NSCLC.