Colorectal cancer (CRC) represents a major health problem in the Western world. Approximately 60% of patients with CRC require systemic therapy for metastatic disease, either at diagnosis or at disease recurrence. Until recently, classic chemotherapeutic agents have been combined in the treatment of advanced CRC. The recent considerable development of novel monoclonal antibodies that target key components of biological pathways has expanded the options to treat advanced CRC patients. These newer agents more specifically target unique features of the cancer cell and its surroundings and so attempt to exploit the progress that has been made in the understanding of basic cell biology. Two targets in particular--the process of new blood vessel development, or angiogenesis, and the EGF receptor and its signalling pathway--are exploited by the newest monoclonal antibodies available for use in this setting. This clinical review focuses on the defining role of the two most clinically advanced novel agents, bevacizumab and cetuximab in metastatic colorectal cancer.