Circulating DNA is present in the blood of all individuals, but it has been found that cancer patients and patients with a variety of other conditions have increased amounts of these circulating DNA fragments in their blood. Even though more than 30 years of research have been done on this subject, the origin of these nucleic acid molecules is still not clear. We present evidence that does not support the general notion that apoptosis or necrosis is the major source of circulating free DNA. Active release of free circulating DNA by living cells may be a plausible mechanism. Disturbance of the equilibrium between the release of DNA by living cells and the mechanisms used for clearing this DNA may play the main role in the appearance of increased amounts of circulating DNA in the blood of individuals with different ailments. Elucidating the origin and the mechanism that cells use to release free circulating DNA into the blood may enhance the diagnostic and prognostic value of these nucleic acid molecules.