Background: Nearly 900,000 patients worldwide have end-stage renal disease and require dialysis or kidney transplantation, and this number is expected to more than double by 2010, placing considerable stress on healthcare systems throughout the world. Despite the availability of these forms of renal replacement therapy for nearly four decades, mortality and morbidity is high and patients often have a poor quality of life. Methods: We have developed a human nephron filter (HNF) utilizing nanotechnology that would eventually make feasible a continuously functioning, implantable artificial kidney. The device consists of two membranes operating in series within one device cartridge. The first membrane mimics the function of the glomerulus, while the second membrane mimics the function of the renal tubules. Findings: The device has been computer-modeled and operating 12 h/day, 7 days/week, the HNF provides the equivalent of 30 ml/min glomerular filtration rate (compared to half that amount for conventional thrice weekly hemodialysis). Conclusions: The HNF system, by eliminating dialysate and utilizing a novel membrane system created through applied nanotechnology may represent a breakthrough in renal replacement therapy based on the functioning of native kidneys. The enhanced solute removal and wearable design should substantially improve patient outcomes and quality of life.