Colorectal cancer is a leading cause of cancer-related deaths, and the two most important considerations for avoidance of this disease are early detection and prevention. If metastasis has occurred to distant sites, such as the liver and lung, the 5-year survival rate for colorectal cancer is below 10%, but this increases to greater than 90% when the cancer is found early. Early detection can be facilitated by use of the digital rectal exam, fecal occult blood test, sigmoidoscopy, and colonoscopy, but these methods might be supplemented in the future by other screening assays using intermediate biomarkers. One interesting biomarker, the aberrant crypt focus (ACF), has been observed in resected human colons, and is the earliest detectable morphological change in the colons of experimental animals treated with carcinogens such as the cooked meat heterocyclic amines. The ACF can also be used as an end-point to screen for potential inhibitors of colorectal cancer; using this approach, we identified conjugated linoleic acids, indole-3-carbinol, chlorophyllin, and tea polyphenols as promising inhibitors in the colon. These compounds can be added to a growing list of natural and synthetic agents that might be effective against colorectal cancer, including selenium, calcium, and nonsteroidal anti-inflammatory agents. However, results from human clinical trials with several of these compounds have highlighted the need for detailed mechanism data before recommendations can be made for wide-scale use in humans. In the meantime, the best approach to reducing the risk of colorectal cancer would be to increase the dietary intake of fruits, vegetables and cereals, while reducing the overall intake of fat, particularly from animal sources.