Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for patients with locally advanced rectal cancer. Controversy on whether patients should receive radical surgery after pathological complete response (pCR) after neoadjuvant chemoradiotherapy has remained since pCR patients have shown favorable long-term outcome. Progress in multidisciplinary modalities has been made, including MRI, PET/CT imaging studies, genetic expression profiling, etc. The methods of predicting pCR response are inspiring. In this article, we review the methods for prediction and prognostic effect of pCR response when patients with locally advanced rectal cancer are treated with neoadjuvant chemoradiotherapy.