On-line HDF represents a major technical development in the delivery of hemodialysis therapy: It combines the properties of increased diffusion available in current high-flux membranes with convective removal of between 6 and 30 liters per treatment and requires the use of ultrapure water and online filtration of replacement fluid. On-line HDF has been successfully introduced in Europe and Asia and is routinely prescribed for dialysis patients in these regions. The book at hand summarizes the history and achievements of on-line HDF in four parts: A report of the technological development in both machine and fiber/dialyzer is followed by a description of the challenges encountered in the evolution of on-line HDF, collecting the accounts of clinical key opinion leaders who had been involved in its early application. The third part presents a comprehensive review of the clinical results achieved with on-line HDF from its inception to the present times, in which it represents the clinical golden standard. The fourth and final part is dedicated to on-line HDF as a ‘vision’ for the future.