Patients with unresectable stage III nonsmall cell lung cancer (T4, N3, or bulky N2) live longer if they receive chemotherapy before or concurrent with thoracic irradiation. Randomized clinical trials have shown that concurrent chemoradiation is superior to sequential chemotherapy followed by radiation, with a 20% reduction in the risk of death compared with the sequential approach. However, concurrent chemoradiation is more toxic than the sequential approach, with an increased risk of radiation esophagitis, pneumonitis, and cytopenias, including febrile neutropenia. The phase III trials showing the superiority of the concurrent approach all used cisplatin-based chemotherapy and enrolled patients with a good performance status. For patients who are not eligible for cisplatin, or who have a poor performance status, weight loss, or poor lung function, a sequential approach may be used with full doses of chemotherapy followed by radiation. Another approach currently being studied in phase III trials is to use lower doses of chemotherapy concurrent with radiation followed by full-dose chemotherapy after radiation, so-called concurrent followed by consolidation therapy. Treatment should be planned by the radiation and medical oncologist with careful selection of approach based on the patient's fitness, comorbid medical illness, and size and location of the tumor. The goal of treatment is to maximize efficacy and minimize toxicity that may interfere with delivery of drug or radiation. In the future, more effective, less toxic chemotherapy drugs and better radiation techniques should improve outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC).