During the past eight years, there have been significant advances in the treatment and outcome of patients with metastatic colorectal cancer. This is likely the result of improved imaging, staging, chemotherapy, and surgery. After conducting a standardized MEDLINE literature search, this article reviews the prospective randomized controlled trials in advanced colorectal cancer published between May 2001 and October 2008. There are a total of 96 studies, all chemotherapy-related trials, divided into five categories based on trial focus: (1) types of chemotherapy; (2) administration of adjuvant or neoadjuvant chemotherapy for resectable liver metastases; (3) regional chemotherapy with hepatic arterial infusion; (4) molecular markers of chemotherapy efficacy; and (5) duration, dosing, and sequencing of chemotherapy.