Circulating tumor DNA (ctDNA) has emerged as a promising and versatile biomarker in colorectal cancer (CRC), providing real-time insights into the tumor burden, minimal residual disease (MRD), and treatment response across both early and metastatic stages. In patients with resected stage II–III CRC, post-operative ctDNA positivity is a robust predictor of recurrence and may outperform traditional clinicopathologic risk factors. It can facilitate adjuvant therapy discussions; however, treatment escalation or de-escalation based solely on ctDNA results is not yet supported by available interventional data. In the metastatic setting, ctDNA-based techniques could provide non-invasive molecular profiling and a monitoring response to systemic therapies. Peripheral blood-based techniques could also help detect emerging resistance to systemic therapy. Emerging evidence highlights that quantitative assessment of ctDNA dynamics, including the baseline burden and post-treatment clearance, could further refine risk stratification and inform treatment personalization. Collectively, ctDNA represents a promising and evolving biomarker with well-established prognostic and emerging predictive potential and is poised to support precision oncology across the continuum of CRC.