In the United States, colorectal cancer is the third most commonly diagnosed cancer and the second most common cause of cancer death. The annual incidence has decreased since the 1980s. However, in the past 25 years, the incidence in adults 40 to 49 years of age, although low, has increased by 15%. The US Preventive Services Task Force recommends that adults with average risk and no signs or symptoms of colorectal cancer undergo periodic screening from 45 to 75 years of age. Starting screening or surveillance at an earlier age should be considered in patients with a prior diagnosis of adenomatous polyps or inflammatory bowel disease, a history of radiation to the abdomen or pelvis to treat a prior cancer, any genetic disorder that predisposes the patient to a high lifetime risk of cancer, or a first-degree relative with colorectal cancer or adenomatous polyps. Recommended screening modalities include stool-based fecal immunochemical tests, which can also include DNA analysis, and direct visualization via computed tomography colonography, flexible sigmoidoscopy, or colonoscopy. Blood-based testing has low sensitivity and high cost and is therefore a second-line screening option performed only when the patient declines all first-line tests. Physicians should emphasize to patients that regular screening is a powerful tool for preventing colorectal cancer and highlight modifiable risk factors, which include staying at a healthy weight; performing moderate to vigorous physical activity; eating a diet high in fruits, vegetables, and whole grains and low in red and processed meats; not drinking alcohol; and not smoking.