Colorectal cancer remains the second leading cause of cancer-related death in the United States. While chemo- therapy remains the backbone upon which treatment for meta- static colorectal cancer is built, targeted therapies have been employed, albeit with mixed results, in the management of this disease. Nonetheless, increased understanding in recent years of the complexity and heterogeneity of cellular abnormalities driving these tumors has identified potential targets for future interven- tions. This article will review the seminal biomarkers of predic- tive and prognostic importance currently used in the treatment of patients with colorectal cancer, and will highlight additional promising biomarkers which may be incorporated into clinical practice in the future.