Targeted biologic therapy remains a very active and evolving field since the US Food and Drug Administration approved cetuximab, a recombinant, human/mouse chimeric monoclonal antibody against the endothelial growth factor receptor, and bevacizumab, a humanized monoclonal antibody directed against vascular endothelial growth factor, for the treatment of colorectal cancer. Benefits of these reagents in diverse clinic settings combined with different chemotherapeutic agents are being defined. Current research is focused on defining which patients will benefit from these treatments and how best to use them in the clinic. Additional preclinical and clinical studies will enable better usage of these biologic agents and lead to the development of new targeted therapies for the treatment of colon cancer.