Chemotherapy now has an established role in the treatment of non-small cell lung cancer, with randomised evidence supporting a survival benefit in both advanced disease and the adjuvant setting. The availability of newer cytotoxic agents has not led to further improvement in outcome, and novel approaches a re needed. Growth factor-mediated signalling pathways are frequently subverted in human cancers, so that physiological processes become abnormally regulated by oncogene products such as epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF). Drugs targeting EGFR and VEGF have already demonstrated improved survival compared with standard of care in lung cancer, and the evidence supporting the use of these and related agents is reviewed here. These newer agents are in general cytostatic rather than cytotoxic, so that clinical benefit can be associated with stable disease rather than with disease response alone, and the impact of this on imaging modalities used to assess response in trials and clinical practice is discussed.