Although there is broad agreement on management options for treating different stages of non-small cell lung cancer (ie, surgery for stage I and II disease, combined treatment modalities for stage III disease, and platinum-based chemotherapy as initial treatment for appropriate patients with stage IV disease), there is considerable geographic variation in practice patterns. These variations reflect a number of factors, including health care economics, the influence of national and regional regulatory bodies, the nature of physician and patient interaction, and probable biological differences between different populations in terms of drug metabolism and inherent susceptibility to both drug activity and toxicity. The approaches taken by three different geographic regions, the United States, European Union, and Japan, are evaluated. Clinically, the most striking differences in activity and toxicity between different regions have been seen with the epidermal growth factor receptor inhibitors gefitinib and erlotinib. Japanese patients experience significantly greater response and a greater degree of interstitial lung disease than patients in the European Union and North America (ie, US and Canada). Similar differences in efficacy and toxicity have also been noted with cytotoxic chemotherapy agents in the first-line setting. These geographic and ethnic differences in toxicity and efficacy will need to be considered in the design and comparison of future clinical trials.