Colorectal cancer (CRC) is a significant health burden worldwide. Despite advancements in treatment options, improvements in CRC patient survival have been limited owing to lack of early detection and limited capacity for optimal therapeutic decision-making. Biomarkers to improve CRC diagnosis, prognosis and prediction of treatment response therefore represent opportunities to improve patient outcome. In addition to genetic alterations and genomic instability, it is now clear that epigenetic alterations play dramatic roles in driving tumor onset and progression in CRC. A recent surge in investigation of epigenetic biomarkers including DNA methylation, miRNA expression and histone modifications has demonstrated that these alterations may be enticing translational biomarker candidates in CRC. In particular, methylation kits have already been incorporated into clinical practice for a handful of cancers, including CRC. This review will aim to summarize the established and emerging roles of epigenetic modifications in CRC detection, prognostication and prediction of treatment response.