In the third millennium preventive medicine is becoming a corner stone in our concept of health. Colorectal cancer (CRC) fits the criteria of a disease suitable for prevention interventions. It is a prevalent disease that is associated with considerable mortality and morbidity rates, with more than 1,000,000 new cases and 500,000 deaths annually. CRC has a natural history of transition from precursor to malignant lesion that spans, on average, 10-15 years, providing a window of opportunity for effective interventions and prevention. Indeed, CRC is preventable in up to 90% of the cases. Simple life style modifications (balanced diet avoidance of smoking and alcohol, and moderate physical activity) can prevent up to 50% of the cases of colorectal cancer. Compliance with current screening methods is a major barrier to the achievement of optimal results, a large part of the average risk population has not been screened by any method. Several newly developed screening modalities, such as the virtual colonoscopy and stool genetic testing may improve compliance. In addition, chemoprevention, a new science that has emerged during the last decade, presents an alternative approach to reducing mortality from colorectal cancer as well as other cancers. Chemoprevention involves the long-term use of a variety of oral agents that can delay, prevent or even reverse the development of adenomas in the large bowel. In light of the recent evidence of the efficacy of chemoprevention in persons at high risk for CRC cancer, it seems only appropriate to consider similar strategies for the general population.