Cell-free circulating DNA containing tumor-specific sequences can be identified in the plasma of cancer patients. Serial analysis of ctDNA can allow the evolving genomic landscape of a cancer to be assessed, with many potential clinical applications. Analysis of ctDNA is challenging and requires highly sensitive techniques due to the small fraction of tumor specific DNA present in the circulation, however, the application of next generation sequencing technologies is now providing new opportunities to develop ctDNA as a non-invasive ‘liquid biopsy’ alternative to tissue biopsies for use in cancer diagnostics and management. Recent research has revealed the high sensitivity of ctDNA as a molecular biomarker for disease monitoring in several solid malignancies. Furthermore, serial plasma DNA analysis is now being applied as a noninvasive tool to study genomic evolution during disease progression and treatment. I will present an overview of these recent and exciting developments as well as an update of our current research that is ongoing in this field.