Lung cancer continues to be the leading cause of cancer-related deaths in the western civilization and developing countries. Non-small cell lung cancer (NSCLC) accounts for > 85% of all cases of lung cancer. Since most patients with NSCLC have advanced disease at diagnosis, to date chemotherapy with third-generation platinum-based doublets represents the standard of care. However, a plateau has been reached with the use of cytotoxic chemotherapy in advanced NSCLC. Advances in the knowledge of tumour biology and mechanisms of oncogenesis have granted the singling out of several molecular targets for NSCLC treatment. In particular, the epidermal growth factor receptor (EGFR), a member of the ErbB family and commonly overexpressed in NSCLC, is one of the most studied targets. Overexpression of EGFR has been associated with a poorer prognosis in patients with cancer, therefore its inhibition may lead to the suppression of tumor proliferation improving clinical outcome. Strategies to block EGFR include development of monoclonal antibodies to EGFR, tyrosine kinase inhibitors, ligand-linked toxins, and antisense approaches. This article will focus on cetuximab and other monoclonal antibodies and their applications in the treatment of advanced NSCLC.