One of the more promising chemotherapeutic agents for patients with metastatic colorectal cancer is oxaliplatin (Eloxatin), a third-generation platinum derivative with a unique mechanism of action. Preclinical studies corroborated by results from early trials suggested that oxaliplatin could be particularly advantageous when used in combination with fluorouracil (5-FU)/leucovorin. In addition, early studies of oxaliplatin as monotherapy showed clear activity similar in magnitude to that observed with other active agents. When administered as neoadjuvant therapy in patients with unresectable liver metastases, the responses were substantial enough for some patients to undergo potentially curative hepatic resection. These trials also demonstrated a reasonable safety profile for oxaliplatin. In light of the accumulating data on the use of oxaliplatin in advanced colorectal cancer, the North Central Cancer Treatment Group (NCCTG) and other cooperative groups developed trials to further define the specific therapeutic roles and optimal regimens of oxaliplatin combined with 5-FU and leucovorin, as well as other agents. A number of studies are underway in the United States, including the three-arm NCCTG N9741 trial in patients with previously untreated metastatic colorectal cancer, the NCCTG N9841 trial in patients who progressed on 5-FU/leucovorin, and the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 adjuvant trial for stage II and III colorectal cancer.