The article reviews the advancements and clinical applications of circulating tumor DNA (ctDNA) in cancer management. It highlights the rapid development of molecular methods that enable sensitive detection and monitoring of mutations in ctDNA, which has led to its increasing utility in various stages of cancer patient management, including diagnosis, molecular profiling, treatment monitoring, detection of residual disease, and identification of resistance mutations. The article discusses the potential of ctDNA for earlier diagnosis and screening, as well as its role in non-invasive cancer classification and sub-typing. It also addresses the challenges in detecting mutant DNA in plasma due to technical and biological factors. The biological characteristics of cfDNA and ctDNA are explored, including their release mechanisms, stability, and fragmentation patterns. The article reviews various approaches for ctDNA analysis, ranging from single mutation detection to whole-genome sequencing, and their clinical utility in different cancer types. It emphasizes the importance of optimizing pre-analytical factors and improving analytical sensitivity to enhance the detection of ctDNA. The article concludes by discussing the future directions for ctDNA research, including the need for larger prospective studies and randomized trials to validate the clinical utility of ctDNA in guiding treatment decisions.The article reviews the advancements and clinical applications of circulating tumor DNA (ctDNA) in cancer management. It highlights the rapid development of molecular methods that enable sensitive detection and monitoring of mutations in ctDNA, which has led to its increasing utility in various stages of cancer patient management, including diagnosis, molecular profiling, treatment monitoring, detection of residual disease, and identification of resistance mutations. The article discusses the potential of ctDNA for earlier diagnosis and screening, as well as its role in non-invasive cancer classification and sub-typing. It also addresses the challenges in detecting mutant DNA in plasma due to technical and biological factors. The biological characteristics of cfDNA and ctDNA are explored, including their release mechanisms, stability, and fragmentation patterns. The article reviews various approaches for ctDNA analysis, ranging from single mutation detection to whole-genome sequencing, and their clinical utility in different cancer types. It emphasizes the importance of optimizing pre-analytical factors and improving analytical sensitivity to enhance the detection of ctDNA. The article concludes by discussing the future directions for ctDNA research, including the need for larger prospective studies and randomized trials to validate the clinical utility of ctDNA in guiding treatment decisions.