Non-small cell lung cancer (NSCLC) is a systemic illness. More than half of those patients who present with stage I-IIIA disease and are resected will experience distant relapse. Postoperative adjuvant chemotherapy has been evaluated in several randomized trials but the results of these trials have been inconclusive with increased survival reported in few trials. In resectable stage IIIA NSCLC the findings of three randomized trials have indicated that the survival of these patients is better with neoadjuvant chemotherapy plus surgical resection than with resection alone. Phase II trials using preoperative concurrent chemoradiotherapy have been carried out with encouraging results. The majority of patients with stage IIIA NSCLC require multimodality therapy if they are to achieve a 5-year survival. Combined modality treatment in locally advanced NSCLC continues to evolve and is a subject of ongoing research. One focus for present research is to integrate new active agents into the neoadjuvant setting. Another challenge is to find better treatment approaches in earlier stages of disease. Some data suggest that induction chemotherapy in stage I-II is feasible, does not appear to compromise surgery and yields high response rates. A further aim is to use molecular biological markers of malignancy to identify patients at highest risk of metastatic relapse.