Circulating tumor DNA (ctDNA) is a promising blood based biomarker that is set to revolutionize cancer management. Non-invasive biopsy takes precedence over tissue biopsy for enabling longitudinal monitoring, providing a comprehensive profile of tumor heterogeneity and the ease of repeated sampling. Advanced genomic technologies enable real-time disease monitoring, detect minimal residual disease and recurrence at the earliest stages, the potential time points when treatment significantly reduces morbidity and mortality and enable tailored and personalized therapy. The review highlights evidence from literature that make ctDNA a potential liquid biopsy marker and the clinical utility of the recent techniques that leverage up on ctDNA. © 2020 Elsevier B.V., All rights reserved.