Preoperative radiotherapy represents the standard treatment for patients with locally advanced rectal cancer. Unfortunately, the response of individual tumors to multimodal treatment is heterogeneous and ranges from complete response to complete resistance. This poses a particular problem for patients with a prior resistant tumors because they may be exposed to irradiation, treatment regimens that are both expensive and at times toxic, without benefit. Accordingly, there is a strong need to establish molecular biomarkers that predict the response. Such biomarkers may guide clinicians in choosing the best possible treatment for each individual patient. It is vital to differentiate the molecular biomarkers to deal with the problem. This review summarized the advances in the biomarkers for response to preoperative radiotherapy for rectal cancer.