Radiation therapy combined with chemotherapy has been the cornerstone of treatment of many different solid tumors. Advances in tumor biology have provided new insights of tumor proliferation, metastases, migration and cell cycle regulation and led to the development of molecular targeted agents. The combination radiation with both classical chemotherapeutic agents and the newer targeted agents may translate into better response rates with less local and systemic toxicity and improved overall survival. This presentation will discuss increasing knowledge in molecular tumor biology that has led to the development of molecular targeting agents and how they have been incorporated into schedules involving radiation. At the conclusion of this activity, the learner will be able to do the following: 1.Define the biological rationale for using chemoradiation in different tissue sites. 2. Identify the status and success of current chemoradiation protocols in the clinical. 3. Explain the strategies for new chemoradiation approaches in pre-clinical studies.