Locally advanced rectal cancer (RC) is treated with neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery. Currently, organ-sparing approaches and/or “watch-and-wait” strategies other than unnecessary surgery have been suggested as the best option for patients who achieve complete regression after neoadjuvant treatment. However, patients respond differently to nCRT, hence the urgent need for effective methods to predict whether individual rectal cancer patients could benefit from this treatment. In this review, we summarize the biomarkers reported to be potential predictors of the therapeutic response of RC to nCRT. Biomarkers that are associated with genes, ribonucleic acid (RNA) and proteins are summarized and described first, followed by other types including immune and tumour microenvironment-related biomarkers, imaging biomarkers, microbiome-associated biomarkers, and blood-based biomarkers.