Colorectal cancer (CRC) affects approximately 6% of the US population, with equal distribution between men and women. It is hereditary in a high proportion of cases and is one of the most preventable cancers. Detection and removal of its precursor lesions, the adenomatous polyps, is the foundation of preventive strategies. However, once CRC is diagnosed, surgical resection is the only cure. The likelihood of cure is higher when CRC is diagnosed at an early stage. Dietary and lifestyle modifications have little, if any, impact on CRC. Endoscopy with polypectomy prevents cancer deaths. The most important issues are screening and surveillance by any of the recommended modalities. Remaining concerns include the choice of screening tests, optimal testing intervals, and cost effectiveness. Patients may be stratified by personal and family risk and by the specific strategies used. Newer developments in genetic testing and imaging, including virtual colonoscopy, hold promise for future prevention. Chemoprevention with nonsteroidal anti-inflammatory drugs may have a role in high-risk populations. Colonoscopy is the most effective method of CRC prevention.