The phenomenon of circulating nucleic acids in plasma and serum (CNAPS) has opened many new research lines, which may be framed within two areas of translational research: the development of new techniques for noninvasive prenatal diagnosis; and the study of the pathobiology of many diseases, particularly of cancer. The detection, quantization, and quality analysis of CNAPS have increasingly been found to be interesting and useful in the diagnosis and management of a number of pathologies, at least as complementary tools. The high potential value of CNAPS and the lack of knowledge about their origin and implications have aroused a great interest in many researchers, especially in the last two decades. In fact, in 1999, about 30 published studies focused on this issue, whereas in 2011 it was more than 100.