Colorectal cancer (CRC) is the second leading cause of mortality in western countries. Delayed diagnosis of CRC is among the major reasons for its high mortality rate and progression to advanced stages. Early diagnosis of CRC is considered very important for timely treatment. Therefore, identification of accurate biomarkers holds the potential of laying a structural foundation for successful clinical management. A multistep process including genetic and epigenetic alterations, drives the development of early premalignant lesions to advanced metastatic CRC. These genetic and epi-genetic alterations accumulated over the course of malignant transformation favor the growth of neoplastic cells and an aggressive phenotype of malignant cells. Several epigenetic modifications have been shown to play a critical role in regulating gene expression, not only causing belligerent malignant cells but also impelling the initial stages of oncogenesis. The present review discusses the diagnostic, prognostic, and predictive applications of epigenetic biomarkers along with therapeutic strategies targeting such epigenetic alterations.