Non-small-cell lung cancer (NSCLC) accounts for > 80% of all lung carcinomas, with the majority of patients presenting with late-stage disease. Selection of an appropriate therapy depends on the stage of disease, with treatment of patients with advanced NSCLC often aimed at palliation of symptoms and improving the well-being of patients. Health-related quality of life (QOL) has been largely ignored as an endpoint in clinical trials for NSCLC, but there is increasing acceptance by clinicians and regulatory authorities that alleviation of symptoms and improved health-related QOL should be carefully considered. This article discusses current approaches to measuring health-related QOL. This discussion is followed by a brief review of some of the current treatment options for patients with NSCLC and their effect on health-related QOL.