Gastroenterologists have a primary role in the management of colorectal cancer patients in that they frequently establish the diagnosis, direct or perform tumor staging evaluations, and initiate referrals for oncologic treatment. Several important advances have been made in the adjuvant treatment of colon and rectal cancers and in therapy of metastatic disease. These advances include the development of more effective combination chemotherapy regimens and molecularly targeted antibodies. These antibodies are directed against regulators of angiogenesis (vascular endothelial growth factor) and tumor cell growth (epidermal growth factor receptor) and have been shown to enhance the efficacy of cytotoxic chemotherapy. In the treatment of localized rectal cancer, the integration of chemotherapy and radiation with surgery has resulted in neoadjuvant approaches that achieve improved tumor control, sphincter preservation, and reduce treatment-related toxicities. This review presents an update of the current approach to colon and rectal cancer treatment, highlighting recent chemotherapeutic advances in the management of these highly prevalent malignancies.