John Marshall, MD, and Mark Lewis, MD, discuss how circulating tumor DNA (ctDNA) testing in colorectal cancer offers promising clinical utility across the care continuum, from early detection to treatment monitoring, with trials like BESPOKE and SWOG 80702 demonstrating its potential to guide personalized therapy decisions, predict outcomes based on minimal residual disease status, complement traditional imaging in challenging cases, and transform patient care through a patient-centric approach that requires ongoing research to establish standardized protocols.