Surgery alone is currently still accepted as the principal therapy for cure for patients with localized non-small cell lung cancer. The optimal therapy in locally advanced and unresectable stage III disease remains unclear. The limited performance of each single therapeutic strategy (surgery, radiotherapy, or chemotherapy) in the treatment of locally advanced non-small cell lung cancer accounted for the rationale of the many attempts at improvement by integrating the different approaches. In recent years, to improve clinical outcome, chemotherapy or chemoradiation followed by surgery, and definitive chemoradiation have commonly been used. Despite numerous phase-II trials, little evidence from randomized phase-III trials has been generated. The ongoing randomized trials will probably provide more reliable indications to define the management of the large number of patients with locally advanced disease.