The combination of radiotherapy with chemotherapy is now considered the standard treatment for a number of tumors. However frequently, within radiotherapy as well as medical oncology, considerable skepticism has been expressed about the real impact of this therapeutic modality, in spite of the improvement in terms of outcome seen in numerous trials concerning head and neck, lung, esophageal cancer and tumors of the anal canal, the uterine cervix and pancreas. Considering the evident clinical advantages achieved in the last 2-3 decades, a close collaboration between basic, preclinical and clinical research is desirable to further optimize the outcomes based on the present radiobiological knowledge. As for the preclinical evaluation different methods should be concomitantly used to analyze the pharmacokinetics and mechanism of action; the method of tumor growth delay should be used especially in neoadjuvant clinical settings; the method of tumor control should be used when chemoradiation is aimed at the local cure of the patient independently of subsequent surgery.