Cell-free circulating DNA containing tumor-specific sequences can be identified in the plasma of cancer patients, providing a liquid biopsy alternative to tissue biopsies for monitoring cancer genetic changes over time. Circulating tumor DNA (ctDNA) analysis can allow real-time monitoring of tumor dynamics and treatment response from a simple blood test that is safe, reliable and easy to perform at regular intervals during therapy. Serial analysis of ctDNA provides a unique opportunity to study the evolving genomic landscape of a cancer during therapy, identify the early emergence of treatment resistance and guide targeted therapeutic decisions. The use of ctDNA for molecular disease monitoring has enormous potential to facilitate precision medicine and optimize cancer management across a range of malignancies. A summary of current approaches for ctDNA analysis will be presented, together with an overview of clinical applications for the use of liquid biopsies in cancer management.