Cell free DNAs (cfDNA) are short DNA fragments which are present in all biological fluids and cell culture medium. They were first detected in blood plasma by Mandel and Metais in 1948. cfDNAs are mostly endogenous-derived fragments that are determined in lipid/protein rich complexes or particles with membranes. In healthy individuals, there are small amounts of mono-nucleosome forms of cfDNA in the peripheral circulation. cfDNA can bind to proteins and phospholipids on cell surfaces. This mechanism may related to absorbance and release of cfDNA. Different enzymes such as deoxyribonuclease (DNase) may facilitate the unbounding and recirculation of membrane bound cfDNAs. The investigation of cfDNA that circulates freely in the blood initiated its application in clinical research including diagnosis. Especially, cfDNA in mother’s blood, which originated in fetus, has been in widely used in prenatal diagnosis already. Moreover, cfDNA has been applied in much clinical research, including cancer, organ transplantation, auto-immune diseases, trauma, myocardial infarcts, and sepsis. Although it is extremely useful to analyze cfDNA for certain pathologies and physiological conditions, there is no definite information about their fragment dimensions, origins nor their character. In this review, the possible origins of cfDNA are explored with an overview of the literature regarding cfDNA and also, its role in genometastasis has been investigated. In addition, the rapidly increasing diagnostic use in recent years, especially its advantages in prenatal diagnosis are discussed.