Evidence suggests that locally advanced non-small cell lung cancer may be more effectively treated with induction chemotherapy followed by radiation or concurrent chemoradiation compared with radiation alone. The majority of combined modality regimens evaluated in mature clinical trials incorporated cisplatin-based combinations, but none has incorporated newer active systemic agents or fully examined the potential role of induction chemotherapy followed by concurrent chemoradiation. The Fox Chase Cancer Center and its affiliate network have evaluated induction chemotherapy with paclitaxel plus carboplatin with or without granulocyte colony-stimulating factor priming followed by concurrent systemic chemotherapy and radiation therapy in patients with locally advanced non-small cell lung cancer. The regimen has been well-tolerated and paclitaxel dose escalation continues. The major response to combined therapy was 55% in the first 38 evaluable patients, and the 1-year survival rate is 72%. Median survival is 15 months. The primary toxicity following induction therapy has been myelotoxicity, which has been mild in severity. During concurrent therapy, the major toxicity has been esophagitis; only limited nonhematologic toxicity has been observed. Other studies evaluating different chemoradiation regimens have reported varying results. Paclitaxel/carboplatin-based combinations, administered cyclically at or near full systemic dose in combination with radiation, are feasible. Randomized studies are needed to determine the proper sequencing, potential survival benefits, and relative safety profiles of these combined modality regimens.