In this review we describe what is recently known about the origin of free nucleic acids in human circulation, which processes can cause the elevations of their total concentrations and the alterations in the ratios among different types of circulating nucleic acids in human plasma and serum. We focus on the inflammatory response and apoptosis with regard to changes in the quantity and quality of circulating nucleic acids pool. We discuss the use of cell-free nucleic acids as biomarkers in patients with renal failure not only in hemodialysis but also in peritoneal dialysis with regard to future perspectives on the field of cell-free nucleic acids.