The past 5 years have seen significant developments in the treatment of colorectal cancer (CRC). New chemotherapy agents with activity in CRC have demonstrated an improvement in survival for patients with advanced CRC. Studies now are focusing on combinations and sequences of chemotherapy agents to prolong survival in second- and even third-line therapies. Oral agents have been developed and are being studied in combination chemotherapy regimens. Development of oral combinations should maintain a survival advantage with the added benefit of convenience for the patient. Drugs designed to act on specific cellular protein targets have also shown activity and are being explored further. Researchers continue to pursue immunotherapy and vaccine therapy. Studies are now focusing on how best to use the available agents. These new agents and new combinations of agents and of approaches have led and should continue to lead to improved outcomes in the treatment of patients with CRC.