Biologic agents are drugs that are made by living organisms. A number of these agents are now routinely used in the treatment of metastatic colorectal cancer. These biologic agents block aspects of specific signaling pathways. They are commonly presumed to have a more selective and targeted action in comparison to cytotoxic chemotherapy, although this assumption is not always borne out by data. These agents were developed with the goal of reducing the use of cytotoxic chemotherapy and thereby reducing the associated toxicities, however they are most commonly used concurrently with cytotoxics, and so the older toxicities often remain. This paper will provide a critical overview of the biologic agents that are currently used in the management of metastatic colorectal cancer, focusing on VEGF and the EGF receptor inhibitors. The rationale behind the use of these biologic agents, including the clinical trials incorporating these agents, will be discussed, and the toxicities associated with these agents will also be reviewed.