The introduction of new agents improved chemotherapeutic options in colorectal cancer. Combination therapy with irinotecan or oxaliplatin, both with infusional 5-FU and folinic acid increased response rates to ca. 50% and prolongs--with effective second line therapy--median overall survival to 20 months in patients with metastatic colorectal cancer. Furthermore, the increased response rates allow neoadjuvant treatment of liver metastasis with the aim of a secondary' resection of liver metastasis. Oral 5-FU prodrugs (i.e. capecitabine) are a convenient alternative but have to prove a comparable efficacy to infusional 5-FU. The most recent studies investigated monoclonal antibodies in the treatment of metastatic colorectal cancer. The additional therapy with the VEGF-antibody bevacizumab prolongs survival by more than 4 months compared to chemotherapy alone. The EGF-receptor antibody cetuximab is an effective therapy after progression with irinotecan.