Systemic therapy of advanced colorectal cancer has become a well established and widely accepted approach for advanced colorectal cancer. The results of prospective randomised trials have demonstrated that first and second line chemotherapy improves the outcome compared with best supportive care. With modern chemotherapy concepts, objective response rates of 30-50% and median survival times of 14-17 months can be achieved which is a step ahead in the management of this disease. Moreover, first experiences with 'preoperative' chemotherapy in technically or prognostically not curatively resectable metastases indicate that active chemotherapy regimens may offer a chance for cure in some subsets of patients with liver metastases. It is still a matter of debate whether combination chemotherapy should be used upfront in all patients or whether the same outcome can be achieved with the sequential use of the available drugs. Ongoing and planned trials dedicated to these issues (preoperative therapy, sequential or combination chemotherapy, etc.) will hopefully contribute to a more differentiated and individualised use of the available treatment options.