Treatment options for patients with advanced lung cancer who have received prior chemotherapy are largely palliative, with little hope for cure. Current therapies may provide only modest survival benefits to patients while potentially adding treatment-related toxicities to lung cancer-related symptoms. However, new treatments have been developed that may improve disease-related symptoms and quality of life with only mild toxicities. The Functional Assessment of Cancer Therapy-Lung, a validated, disease-specific quality-of-life instrument, effectively correlates quality-of-life changes with clinical outcomes in patients with non-small-cell lung cancer. In a large randomized trial from the Eastern Cooperative Oncology Group study 5592, a change of two to three points in the Lung Cancer Subscale of the Functional Assessment of Cancer Therapy-Lung was found to be clinically meaningful and correlated well with patient symptom differences at baseline, changes in symptoms after treatment, tumor response, and time to disease progression. Results from trials that include symptom improvement and quality of life as end points, in addition to the more standard outcomes of tumor response and survival, will provide meaningful information in evaluating the clinical benefits of new cancer treatments.