The choice of first-line treatment in metastatic colorectal carcinoma should basically depend on the clinical situation at the time and on the goals of treatment, because independent predictive factors have not yet been established. In patients with potentially resectable liver or lung metastases, the most active available therapy that might allow R0 resection should be given. At present this means a triple combination therapy, either with chemotherapy and a monoclonal antibody or the triple chemotherapy combination FOLFOXIRI. If the primary goal of treatment is the longest possible progression-free survival time, then the scientific and clinical evidence points to using the triple combination with bevacizumab. If there is no prospect at all of successful resection and no tumor-related symptoms are present either, and if at the same time the patient expresses a desire to keep toxic effects to a minimum during the initial phases of therapy, then it is also possible to start treatment with monotherapy and follow this with a sequential chemotherapy regimen, as shown in the CAIRO, FOCUS, and FOCUS2 trials. An alternative option is the combination of bevacizumab plus capecitabin, since the efficacy of this combination with regard to progression-free survival is comparable to that of FOLFOX or of FOLFIRI, but it is considerably better tolerated. Despite this, in most cases priority in the first-line treatment should still be given to combination therapy, since this may also - after a sufficiently long period of treatment and after adequate tumor control has been achieved - offer the opportunity for a treatment pause or deescalation.