Colon cancer is the second cause of death for cancer worldwide. In most cases it is diagnosed when it is still localized to the intestinal wall or in regional lymphnodes. Post-operative systemic therapy with 5-fluorouracil and folinic acid in combination with Oxaliplatin is the standard option for patients with radically resected stage III disease. In stage II, the value of a post-operative treatment remains controversial, but the identification of prognostic factors, histopathological and molecular, may allow the selection of patients who can benefit from adjuvant treatment. The inclusion of molecular targeted agents in combination regimens with cytotoxics, already proven effective in advanced disease, is the main field of development in the most recent protocols of adjuvant therapy.