Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. Almost every second patient dies of the disease. The introduction of new and effective chemotherapeutic substances and biologics in the past decade has significantly improved the systemic treatment of patients with CRC. In stage III colon cancer combination chemotherapy with oxaliplatin is the standard of care. In stage IV cancer the choice of therapy is dependent on the clinical status of the patient. For some patients primary resection of metastases or resection after combination therapy and downsizing of lesions offers a chance for cure. In the palliative setting intensive combination treatment is indicated if the patient suffers from tumor related symptoms or a rapid progress of the disease. The aim of palliative therapy is the prolongation of survival and the improvement of quality of life. Combination with monoclonal antibodies leads to further improvement of survival. Furthermore, the introduction of the mutational status of the KRAS oncogene as the first predictive marker into clinical care is an important step towards the individualization of treatment in CRC.