Cancer-derived cell-free DNA (cfDNA) represents a promising biomarker for sensitive, specific, and dynamic detection of disease burden in cancer patients. Mutations in tumor-derived DNA represent ideal potential biomarkers since they are highly specific to cancer cells and are involved in disease pathogenesis. However, even in advanced cancer patients, concentrations of cancer-derived cfDNA are often low and difficult to detect. In this presentation I will highlight several potential applications of cfDNA analysis in oncology, with a focus on detection and monitoring. I will present data our group has generated using Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq), a sensitive and specific method for detection of cancer-derived cfDNA.