Considerable progress has been made in the past three decades in our understanding of the biology and prevention of colorectal cancer. The long natural history of colorectal cancer as it evolves from adenomatous polyps in the majority of cases provides opportunities for detection of early stage cancer and for prevention of cancer by removal of adenomas. Strong evidence of the effectiveness of screening has resulted in a worldwide consensus, as reported in evidence-based guidelines, that screening should be offered to all men and women age 50 and older, younger in the presence of factors that increase risk. Several options are now available for screening, and the emerging technology of stool DNA testing and virtual colonoscopy shows promise. However, many problems remain to be addressed. Screening rates are low. Successful strategies need to be implemented to overcome patient and system barriers. Resources, especially endoscopic capacity, may be inadequate to handle the burden of screening, diagnosis, and follow-up surveillances. There are quality-control issues at every step. Stratification of people by risk, a two-stage screening approach and less intensive surveillance following polypectomy can be helpful. Colorectal cancer screening is cost-effective and could save many lives each year if it were widely implemented.