About 10% of apparently normal individuals are sensitive to clastogenic effects of physico-chemical agents. More than 45% of breast cancer patients’ exhibit elevated radiosensitivity. Although the nature of inherent radiosensitivity is not fully understood, but insufficiency and impaired DNA repair mechanism might be prime cause of radiosensitivity. This is evident from genetically affected individuals such as ataxia telangiectasia, severe combined immunodeficiency, Xeroderma pigmentasum, Fanconi anemia who show sensitivity to ionizing radiation, ultraviolet light and alkylating agents. All these genetic diseases are caused due to impaired DNA damage repair mechanism. Radiation therapy (RT) is a common and effective way of treatment in several types of malignant tumors. Some cancer patients suffer from side effects of RT such as radiation induced early or late adverse responses in normal tissues within weeks, months, or even years post irradiation, due to intrinsic radiosensitivity. The RT efficiency limitation raises from ionizing radiation toxicity reactions in normal tissues.  An appropriate protocol to prevent or treat these side effects, has not been developed yet. Molecular pathways involved in adverse responses to cancer treatment agents have not been well defined. Identification of molecular mechanisms may be promising to enhance the output of treatment technologies and overall survival of cancer patients. Several techniques such as microarray technology has been used to clarify molecular mechanisms involved in radiosensitivity by finding genes related to RT normal tissue responses. DNA repair, apoptosis, cell cycle, and growth factor associated genes are the most important candidates in this field.