Colorectal cancer is the third most common cancer both in men and women in the United States. Advances in adjuvant treatment of colon cancer have came to consist of a succession of small improvements by large-scale clinical trials. The National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials reflect the exciting history of progress in adjuvant treatment of colon cancer. Since 1977, the NSABP has successfully designed and conducted seven large-scale prospective randomized clinical trials for colon cancers that has altered and improved the standard of care for patients with this disease. More than 5,000 physicians, nurses, and other medical professionals at nearly 200 medical sites from across the United States, Canada, Puerto Rico, Australia and New Zealand assist the NSABP in its mission to eliminate colorectal and breast cancers. These medical sites include several university hospitals and many other local medical centers that treat patients from a variety of social, and economic backgrounds contributed to the trials. The NSABP clinical trials are distinctive because of the large number of patients and elimination of social, cultural and economic influences. The ongoing trials of the NSABP should continue to provide information used to determine principals of neoadjuvant treatment for colon cancer. In this article we review seven prospective randomized clinical trials with their published results and discuss the combined analysis of the first four trials.