Colorectal cancer is the third most common malignant disease in incidence according to a report in 2009 from Korea. The 5-fluorouracil (5-FU) remains to be a major chemotherapeutic agents. But, over the last 10-15 years, the treatment pattern for metastatic colorectal cancer changed significantly. Irinotecan and oxaliplatin are cytotoxic drugs, or bevacizumab and cetuximab are monoclonal antibodies against molecular targets. The introduction of novel agents targeting specific molecular features of cancer cells promises more options and marked improvements in efficacy for the treatment of metastatic colon cancer. Bevacizumab has been shown to extend survival in colorectal cancer when used in combination with irinotecan and 5-FU-based chemotherapy, and the addition of cetuximab to irinotecan and 5-FU-based chemotherapy eliminates irinotecan resistance. Better understanding of the tumor biology and the molecular pathway and mechanisms of tumorigenesis has led to the discovery of novel agents with improved outcomes.