The recent development of drugs that target the key components of biologic pathways rendered an improvement in survival in colorectal cancer patients. Two monoclonal antibodies in particular, targeting vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) – bevacizumab and cetuximab are clinically available. The expectations with low molecular weight tyrosine kinase inhibitors in the treatment of colorectal cancer have not been confirmed. This review focuses on the defining role of the novel targeted agents in colorectal cancer.