A hallmark of locally advanced non-small cell lung cancer is its high local and systemic recurrence rates, ranging from 60% to 80%. Radiotherapy has shown its efficacy in controlling the tumor and in increasing overall survival, especially with combined sequential or concurrent chemotherapy to allow an anti-tumoral synergy. Gemcitabine, a new generation cytotoxic agent, is a potent radiosensitizer in vitro, and thus appears as a promising molecule in these multimodal therapeutic regimens. If the initial trial with gemcitabine and radiation produced unacceptable toxicities, lessons were learned from this study, and further phase I-II trials demonstrated that in a clinical trial setting, gemcitabine and radiation can be given safely, both in sequential and concurrent chemoradiation regimens, leading to high response rates and prolonged survival. Gemcitabine-radiation combination is currently integrated in phase III trials evaluating the optimal therapeutic sequence in locally advanced non-small cell lung cancer, and appears as one of the most promising therapeutic regimen in thoracic oncology.