Non–small cell lung cancer remains the leading cause of cancer death in men and women, with a significant proportion of patients having locally advanced, unresectable disease at the time of diagnosis. Although significant advances in definitive therapy have been made with the concurrent administration of combination cytotoxic chemotherapy and thoracic irradiation, recurrence rates are still high, and long-term survival rates are suboptimal. The application of more modern radiation techniques and the addition of molecularly targeted systemic agents may add further benefit in survival.