The introduction of new agents improved chemotherapy of metastatic colorectal cancer. A combination of infusional 5-FU/folinic acid with oxaliplatin or irinotecan results in markedly increased response rates (ca. 50%). This effective first line therapy, together an effective second line therapy led to an median survival of 20 months and more. The increased response rates allow neoadjuvant treatment of primary non-resectable liver metastasis. Due to the survival benefit, combination first line therapy is the treatment of choice, at least in patients with good performance status. 5-FU prodrugs allow an oral therapy, which is more convenient to the patients. However, efficacy of this monotherapy is limited. Results of recently trials showed antibodies showed promising results: the VEGFR-antibody bevacizumab (in combination with chemotherapy) prolongs survival by more than 4 months compared to chemotherapy alone. The EGFR-antibody cetuximab is effective after progression during irinotecan-treatment.