The treatment of advanced non-small-cell lung cancer (NSCLC) has improved over the past two decades with the availability of new agents such as gemcitabine, the taxanes and vinorelbine. Despite these advances, survival prospects remain disappointingly low for most patients. Further improvements in response rate and survival requires the development of new agents with novel mechanisms of action, such as molecularly targeted therapies, which are currently being tested in clinical trials. The conventional treatment approach to NSCLC is beginning to shift towards the application of specific strategies and techniques, such as pharmacogenomics, to tailor treatment to individual patients. Many efforts are in progress to identify the clinical predictors of outcome. The discovery of prognostic molecular markers, such as the putative suppressor gene (RRM1), represents a novel and potential parameter to help guide clinical treatment decisions.