The preclinical rationale for chemoradiation was demonstrated. While chemoradiation allowed for improved outcome in nonsmall cell lung cancer patients, prognosis of patients remains particularly pejorative, encouraging major expansion of targeted therapies concurrently with radiotherapy. Thorough knowledge in biological mechanisms of oncogenesis permitted identifying new therapeutic targets, for which specific interactions allow pharmacological radiosensitivity modulation. Two modalities of EGFR inhibitors have been developed: monoclonal antibodies and tyrosin kinase inhibitors, which assessement remains at its beginning. Angiogenesis inhibition was also developed, illustrating the absolute necessity for careful clinical assessment. Drugs with multiple targets are becoming available and offer new optimization modalities for radiation therapy.