Transrenal DNA (Tr-DNA) is a recently discovered class of extracellular urinary DNA that originates from cells dying throughout the body. Postapoptotic DNA is known to appear in the circulating plasma, but it is now recognized that a portion of these fragments cross the kidney barrier and appear in urine in the form of 150–200-bp fragments. Tr-DNA containing fetal sequences has been isolated from the urine of pregnant women, tumor-specific mutations have been detected in Tr-DNA from patients with colon and pancreatic tumors, and donor DNA has been found in Tr-DNA isolated from recipient urine. Furthermore, proviral HIV DNA, bacterial and parasite DNA sequences have been detected in Tr-DNA from infected patients. Potential applications of Tr-DNA-based tests cover a very broad area of molecular diagnostics and genetic testing, including prenatal detection of inherited diseases, tumor diagnostics and therapeutic monitoring and detection of infectious agents. The Tr-DNA test is expected to have utility in treatment monitoring, transplantation monitoring, drug development and broad public health screening, where a noninvasive, common-platform diagnostic technology has particular value. This review describes some of the highlights of Tr-DNA technology applications, advantages over existing technologies and potential problems anticipated in test development.