This article will provide an overview of the principal toxicities associated with commonly used chemotherapy treatment regimens for metastatic colorectal cancer (mCRC) and explore the role of the oncology nurse in the management of treatment-associated toxicity. Although patients with mCRC have benefited considerably from recent therapeutic advances, the use of more complex treatment regimens has inevitably resulted in an increase in treatment-related toxicities. This can ultimately lead to dose reductions, delays, or discontinuation of therapy, which may negatively affect efficacy outcomes. Early identification and treatment of toxicities often can allow treatment to continue as planned or at a lower dose, if required. The oncology nurse is ideally positioned to assist with the timely recognition and management of side effects. This allows therapy to be continued on schedule and at the appropriate dose, enabling patients to achieve a better clinical outcome and maintain or improve their quality of life.