Colorectal cancer (CRC) is a heterogeneous disease entity in terms of both molecular carcinogenesis and morphologic carcinogenesis multistep pathways. Considerable heterogeneity exists within CRC due to the varied genetic and epigenetic mechanisms involved in different carcinogenesis pathways. A better understanding of pathophysiology of tumors is necessary to develop modern and successful means of treatment in metastatic CRC. Over the last 5 years, there has been a surge in interest in the molecular classification of colorectal cancer, as its clinical importance both for predicting prognosis and in guiding personalized treatment had been acknowledged. Recently, the Colorectal Cancer Subtyping Consortium identified four consensus molecular subtypes, CMS 1-4 in CRC; however, attempts to stratify CRC using molecular features for prognostic and predictive purposes in clinical conditions had limited success. In this review, we focused on molecularly defined subtypes of CRC including specific mutations and discuss implications for current and future patient management in metastatic CRC to achieve the maximal therapeutic response for each patient, while reducing adverse side effects of therapy.