The therapeutic choice for patients with mCRC is becoming harder because of the availability of four chemotherapic agents and five biological drugs. The therapeutic approach requires the definition of the strategy that must consider the tumor and the patients features. Following the decision on how to start treatment, we also need to consider that the choice includes various other factors: how to continue first-line treatment after induction therapy, how to carry on maintenance therapy, when it is possible to talk about second-line, biological drugs: which one and when, metastasis resection: when. All these key issues have been discussed by an Internationally renowned panel.