Since cancer biology is now better understood, molecular targets involved in tumorigenesis have been identified and specific "targeted therapy" has been designed. Antiangiogenic and anti-EGFR are the 2 targeted families of drugs introduced in the management of colorectal cancer. Bevacizumab, cetuximab and panitumumab are well tolerated and improve the pronostic of the patients in combination with conventional chemotherapy. Moreover, the mutation of KRAS gene has been recently identified as a predictive factor of resistance to anti-EGFR and allows a better selection of the patients. Formely based on 5FU, the management of advanced colorectal cancer is now involving a complex multidisciplinary strategy combining conventional chemotherapy, targeted agents, and surgery with curative intent whenever possible.