Lung cancer is the leading cause of cancer deaths. Non-small cell lung cancer constitutes approximately 75% of lung cancers, and 40% present as advanced stage IIIa or IIIb, where primary surgery is ineffective. Radiation of the primary tumor and the regional lymphatics has been the traditional treatment for unresectable locally advanced disease, but few patients achieved a complete response. Because of the limited benefits provided by radiation therapy, the use of combined chemoradiotherapy in patients with locally advanced, unresectable NSCLC was explored. Combined chemoradiotherapy appears to have improved the outcome of patients with locally advanced unresectable stage III NSCLC, with a median survival of 13 to 14 months and 5-year survival rates as high as 15% to 20%, nearly three times that reported with radiation therapy alone and various agents have been used either sequentially or concomitantly in clinical trials of combined chemoradiotherapy for NSCLC. The interactions of chemotherapy and radiation therapy are complex. The texanes interact with radiation at many levels. Cell-cycle synchronization through mitotic arrest has been consistently shown to have a major role in radiation enhancement, but increased apoptosis and tumor reoxygenation may constitute additional mechanisms. Clearly, the interaction is multifactorial and the dominant mechanism may be affected by specific settings that include drug exposure and concentration, tumor type, and radiation dosimetry.