Dennis’ group reported the presence of cell-free fetal DNA in maternal plasma in 1997. Since then, this technology has been developed into a platform for noninvasive prenatal testing (NIPT) that can be used for the screening of multiple types of fetal chromosomal aneuploidies, various types of single gene disorders and even for fetal whole genome sequencing. Apart from circulating fetal genetic markers, recent work has also led to the development of fetal epigenomic and transcriptomic analyses from maternal plasma. Excitingly, the global success of NIPT has triggered researchers in other fields to explore the use of circulating nucleic acid technology in multiple areas, notably in the liquid biopsy of cancer. Circulating nucleic acid technology has therefore brought about a paradigm shift in diagnostic medicine.