The majority of patients with non-small cell lung (NSCLC) cancer are not candidates for curative resection because they present with either locally advanced or widely metastatic disease. As a result of improved survival observed with chemoradiation in phase III trials [l-3] and in a meta analysis [4]. Combined modality treatment has replaced radiation alone as the primary treatment for locally advanced NSCLC. Although most physicians treat good performance status stage III NSCLC patients with combined chemotherapy and radiation, issues regarding the optimum doses and schedule for chemoradiation are not resolved. Three randomized trials [l-3] comparing 2-3 courses of platinum containing combination chemotherapy regimens given prior to thoracic radiation compared to radiation therapy alone provided the first evidence that combined chemotherapy and radiation resulted in a modest improvement in long term survival compound to radiation alone. During the last decade there have been at least four randomized trials [5-81 which evaluated either cisplatin or carboplatin as a single agent given in radiation sensitizing doses concurrently with thoracic radiation. In one of the studies treatment with cisplatin and concurrent split course radiation was associated with significantly longer survival compound to radiation alone [5] The survival difference appeared to be due to a reduced rate of local failure [5]. In contrast, the remaining three trials failed to show a significant difference in survival in patients treated with a platinum compound [6-81. Full doses of older platinum containing regimens have been given either concurrently or sequentially in two phase III trials [9,10]. In each study improved survival was observed in patients treated with simultaneous chemoradiation. In the more mature trial the 5 year survival rate with simultaneous chremoradiation was 16% compared to 9% for sequential chemoradiaton [9]. Choy et al demonstrated that it is feasible to combine thoracic radiation with radiation sensitizing doses of paclitaxel and carboplatin [ 111. Preliminary analysis of a randomized phase II trial [ 121 testing various paclitaxel-carboplatn-radiation schedules suggest that the most favorable survival results were observed in patients treated initially with concurrent chemotherapy and radiation. Important information will be obtained from the recently completed phase III CALGB trial in which one group of patients received radiation sensitizing doses of paclitaxel-carboplatin and concurrent thoracic radiation initially, while the other group of patients received two full courses of paclitaxel-carboplatin followed by the same concurrent chemoradiation regimen. CALGB investigators have also conducted a randomized phase II trial comparing two courses of chemotherapy followed by lower doses of the same regimen given concurrently with chest radiation [13]. None of the three chemotherapy regimens (gemcitabinecisplatin, paclitaxel-cisplatin, and vinorelbine-cisplatin) could be used simultaneously at full dose with thoracic radiation [3]. The SWOG has conducted two consecutive, relatively large phase II trials in which full doses of cisplatin-VP16 were given simultaneously with thoracic radiation. In the more recent trial patients received three courses of docetaxel following completion of cisplatin-VP16-radiation [ 141. The survival results (median survival-27 months, 3 year survival-40%) were encouraging [ 141, and this observation has resulted in this regimen being chosen as the comer stone for testing on EGFR inhibitor, gefitinib, in a SWOG locally advanced NSCLC trial comparing gefitinib or placebo following completion of chemo-radiation and docetaxel. Currently it appears that giving full dose, older chemotherapy regimens simultaneously with thoracic radiation is the most effective treatment for good performance stage III NSCLC patients. The optimum way of intergrating thoracic radiation with newer cytotoxic and biologic targeted agents remains to be determined.