Multiple approaches of combined modality therapy have emerged as potential treatments for improving unresectable, locoregionally advanced non-small-cell lung cancer (NSCLC). Several agents have been used either sequentially or concurrently in clinical trials of combined chemoradiotherapy. However, no specific regimen has been clearly defined, particularly with regard to the timing of chemotherapy (sequential and/or concurrent), the specific chemotherapeutic drugs, and the dose and intensity of the radiation therapy. Concurrent chemoradiotherapy demonstrates a survival advantage compared to sequential chemoradiotherapy. Initial data suggest that induction chemotherapy prior to concurrent chemoradiotherapy does not further improve survival. The potent radiosensitizer gemcitabine has been evaluated in combination chemotherapy with radiation therapy and appears to be a promising agent, although further trials are needed to define its optimal dose, toxicity and efficacy.