Chemotherapy for advanced colorectal cancer is much improved in this decade. Biochemical modulation and multi-drug therapies, such as FOLFOX, FORFIRI and IFL, contributed to higher response rate and prolonged patient's survival. It was recommended to administer oxaliplatin with 5-FU and leucovorin in first line chemotherapy and CPT-11 for the second line, or in reverse sequence. 5-FU+l-LV and UFT+LV are still common first line therapies and CPT-11 as a second line in Japan, as oxaliplatin, capecitabine and molecular target agents are not available. Physicians should consider maintaining good QOL of the patient, as well as tumor shrinkage and prolonged survival, in second line chemotherapy.