The detection of cell-free RNA in the plasma and serum of human subjects has opened up new investigational opportunities. Tumor-derived RNA was detected in the plasma and serum of patients with various forms of cancer. Through the development of robust extraction and quantification protocols for circulating RNA, new information regarding its biology and characteristics has been obtained. Plasma RNA was shown to be particle associated and to be surprisingly stable. Recently, fetal RNA was also demonstrated in maternal plasma. The placenta was shown to be an important source of such circulating fetal RNA. This discovery has created new prenatal diagnostic and monitoring possibilities. It is expected that circulating RNA will find application in many other clinical scenarios, including emergency medicine.