Radiochemotherapy represents the cornerstone of the treatment for patients affected by locally advanced non small cell lung cancer. Nevertheless, to date there is no agreement concerning how the standard therapy is and many questions are still open. Two timing modalities have been proposed to combine chemotherapy and radiotherapy: after many phase II/III have tested concurrent or sequential approach, concurrent radiochemotherapy is today considered as the treatment of choice, despite the role of induction or consolidation chemotherapy is still unclear. Cisplatin alone or in combination is considered as the reference drug in combination with chemotherapy, but in the last decades, many trials have demonstrated that new-generation drugs, which are routinely used in metastatic disease, may be used during radiotherapy and may enhance its tumor control rate, frequently having a radiosentizing power. Finally, in the era of molecular biomarkers and target therapies, new approaches could dramatically change the physicians view about the drug choice giving the opportunity of a tailored therapy customized on the single patient also in the treatment of locally advanced non-small cell lung cancer.