Nearly one third of non-small cell lung cancer (NSCLC) patients at diagnosis have stage III disease. Concurrent chemoradiation has emerged as the standard of care for patients with unresectable stage III NSCLC. Meta-analyses of studies comparing concurrent with sequential therapy showed that there was a relative improvement of about 20% with concurrent therapy over sequential therapy in these patients and that concurrent chemoradiation is more toxic than the sequential approach, particularly with regard to esophagitis. The incidence of pneumonitis is not significantly higher with concurrent therapy. All the phase 3 trials comparing concurrent with sequential therapy included cisplatin-based therapy. In addition, patients enrolled in these studies were required to have good performance status and some studies mandated limited weight loss. Some patients are also treated with lower doses of chemotherapy, particularly carboplatin and paclitaxel, concurrently with radiation followed by full-dose chemotherapy. Randomized studies have failed to show benefit of induction or consolidation chemotherapy. For patients who have a poor performance status or significant weight loss, a sequential approach of chemotherapy followed by radiation may be appropriate. Ongoing clinical trials are evaluating the utility of integrating some of the newer agents such as pemetrexed and cetuximab into the treatment plan for stage III patients.