Purpose of Review <p>Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Liquid biopsy by peripheral blood circulating tumor DNA (ctDNA) measurement has emerged as a promising biomarker in the management of CRC. We aimed to summarize the current landscape of ctDNA assessment in CRC by briefly addressing relevant technicalities of ctDNA assays, reviewing the current body of evidence regarding the utility of ctDNA across the clinical spectrum, and providing considerations and prospectus for the future of ctDNA in CRC.</p> Recent Findings <p>Data from prospective trials investigating the use of ctDNA in CRC is rapidly accumulating. Positive ctDNA status is a strong prognostic factor for recurrence, now recognized in cancer treatment guidelines, and is emerging as a potential guide for adjuvant therapies in the setting of resected localized and metastatic disease. Mounting evidence also suggests that ctDNA measurement can potentially have a meaningful impact for CRC screening, multi-cancer early detection, and longitudinal surveillance of tumor biology in the setting of systemic therapies such as anti-EGFR rechallenge. There is a paucity of randomized controlled trial data supporting ctDNA use.</p> Summary <p>ctDNA assessment may improve the clinician’s ability to gain granular information about tumor biology and activity across the spectrum of CRC. The results of ongoing randomized trials will further inform the value of routine ctDNA testing while helping steer future investigation</p>