Colorectal cancer is a leading cause of cancer death world-wide. There have been important advances in the chemotherapeutic management of colorectal cancer as a result of a deliberate collaborative process of well-designed clinical trials. From the earlier standard of 5-fluorouracil-based therapy alone, the recent availability of newer agents, including capecitabine, irinotecan and oxaliplatin, has significantly expanded the options available for the management of patients with advanced colorectal cancer, with consequent improvements in survival. For patients with resected, high-risk, localized disease, adjuvant systemic chemotherapy improves survival. The identification of new chemotherapy regimens, the use of predictive testing and the integration of novel targeted therapies with cytotoxic chemotherapies are areas of active clinical investigation. A review of the chemotherapeutic management of colorectal cancer is presented.