Systemic chemotherapy is the standard treatment for patients with advanced stage non-small cell lung cancer (NSCLC) and improves both their survival and quality of life. Despite this, the overall prognosis for advanced NSCLC remains poor. Molecularly targeted therapies are being developed in an effort to improve outcomes for patients with advanced NSCLC. The epidermal growth factor receptor (EGFR) pathway is dysregulated in the majority of NSCLC tumors and plays a role in tumor growth and invasion. As such, EGFR has emerged as a rational target in the treatment of NSCLC. EGFR signal may be blocked with small molecule inhibitors of the tyrosine kinase of EGFR (erlotinib, gefitinib) and with monoclonal antibodies against the ligand-binding domain (cetuximab). Erlotinib and gefitinib are in clinical use as single agents for the treatment of NSCLC and recent data suggest cetuximab improves survival when combined with chemotherapy for the treatment of metastatic NSCLC. This article reviews the role of currently available and emerging EGFR inhibitors in the treatment of NSCLC.