Liquid biopsy is a term used to describe non-invasive tests, which provide information about disease conditions through analysis of circulating cell-free DNA and circulating tumor cells from peripheral blood samples. In patients with cancer, the concentration of cell-free DNA increases, and structural, sequence, and epigenetic changes to DNA can be observed through the disease process and during therapy. Furthermore, cell-free DNA released by the tumor contains the same variants as those in the tumor cells. Therefore, cell-free DNA allows non-invasive assessment of cancer in real time. This review summarizes the origin of cell-free DNA, recent advancements in the detection of cell-free DNA, a possible role in metastasis, and its importance as a non-invasive diagnostic assay for cancer.