The colorectal cancer (CRC) subtyping consortium has unified six independent molecular classification systems, based on gene expression data, into a single consensus system with four distinct groups, known as the consensus molecular subtypes (CMS); clinical implications are discussed in this review based on articles relevant to the CMS of CRC indexed in PubMed as well as the authors’ own published data. The CMS were determined and correlated with epigenomic, transcriptomic, microenvironmental, genetic, prognostic and clinical characteristics. The CMS1 subtype is immunogenic and hypermutated. CMS2 tumors are activated by the WNT-β-catenin pathway and have the highest overall survival. CMS3 feature a metabolic cancer phenotype and CMS4 cancers have the worst survival and have a strong stromal gene signature. The CMS of CRC may better inform clinicians of prognosis, therapeutic response, and potential novel therapeutic strategies.