DESCRIPTION: Colorectal cancer (CRC) is a leading cause of morbidity and cancer-related mortality in the United States. Despite multiple screening options, adherence to CRC screening in the United States remains suboptimal, and there are racial, ethnic, and geographic disparities in CRC screening rates and outcomes. Advances in diagnostic technology have allowed for development and validation of blood tests for CRC screening. In this Clinical Practice Update, our aims were to review the current evidence on blood tests and the potential implications for CRC screening. We leveraged published modeling studies to understand the optimal test performance characteristics, interval, and uptake that would be needed for blood tests to achieve comparable effectiveness to that of currently available stool tests and screening colonoscopy. METHODS: This expert review/commentary was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The manuscript underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology.