Opinion statementColorectal cancer (CRC) imposes significant morbidity and mortality, yet it is also largely preventable with evidence-based screening strategies. In May 2021, the US Preventive Services Task Force updated guidance, recommending screening begin at age 45 for average-risk individuals to reduce CRC incidence and mortality in the United States (US). The Task Force recommends screening with one of several screening strategies: high-sensitivity guaiac fecal occult blood test (HSgFOBT), fecal immunochemical test (FIT), multi-target stool DNA (mt-sDNA) test, computed tomographic (CT) colonography (virtual colonoscopy), flexible sigmoidoscopy, flexible sigmoidoscopy with FIT, or traditional colonoscopy. In addition to these recommended options, there are several emerging and novel CRC screening modalities that are not yet approved for first-line screening in average-risk individuals. These include blood-based screening or "liquid biopsy," colon capsule endoscopy, urinary metabolomics, and stool-based microbiome testing for the detection of colorectal polyps and/or CRC. In order to maximize CRC screening uptake in the US, patients and providers should engage in informed decision-making about the benefits and limitations of recommended screening options to determine the most appropriate screening test. Factors to consider include the invasiveness of the test, test performance, screening interval, accessibility, and cost. In addition, health systems should have a programmatic approach to CRC screening, which may include evidence-based strategies such as patient education, provider education, mailed screening outreach, and/or patient navigation, to maximize screening participation.