Evidence-based guidelines recommend that all asymptomatic, average-risk U.S. citizens >50 years of age be encouraged to undergo screening for colorectal cancer. Those at higher risk should be offered more intensive screening and follow-up surveillance. It is estimated that widespread adoption of these recommendations could reduce mortality from colorectal cancer by >50%. The only screening methods that have been evaluated directly are the fecal occult blood test and flexible sigmoidoscopy. Current guidelines now recommend annual screening for fecal occult blood plus flexible sigmoidoscopy every 5 years for asymptomatic, average-risk men and women >50 years of age. Indirect evidence supports the options of colonoscopy or barium enema x-ray screening for highly motivated individuals, but these methods have not yet been tested in prospective trials. In the future, gene-based screening tests may be developed, and computed tomography of the colon (“virtual colonoscopy”) may prove effective and feasible.