Despite recent advances in current chemotherapy, the prognosis for locally advanced and metastatic nonsmall-cell cancer remains poor, and new approaches are required. An increased understanding of the biology of lung cancer has identified pathways mediated by receptor tyrosine kinases as an important target. The epidermal growth factor receptor (EGFR) is frequently expressed on the surface of the lung cancer cell. EGFR can be targeted by inhibitors of receptor tyrosine kinase activity such as erlotinib and gefitinib and by antibodies specific for the extracellular domain. Subset analysis of responders to the receptor tyrosine kinase inhibitors suggests that clinical benefit may correlate with the presence of EGFR mutations. Other drugs in earlier clinical development include those directed against HER-2, VEGF, farnesyl transferase, COX-2 and retinoid receptor.