Renal replacement therapy (RRT) has reached its plain maturity. RRT is an unavoidable and banal tool in the armamentorium in the treatment of end stage renal failure (ESRD). It relies on several practical modalities (hemodialysis, peritoneal dialysis and their variants) that permit to satisfy various patient's needs and to ensure the continuity of life support system. Substitution of certain renal endocrine functions (human recombinant erythropoietin, active vitamin D) has brought a new dimension to the treatment of ESRD in improving substantially the quality of life of these patients. Now, if the long-term outcomes confirm the high efficiency of the renal replacement therapies they also draw their limits bounded by the occurrence of a specific pathology of the "long term dialysis" patient. Such dialysis-related pathology is clearly the new challenge for the nephrologist in the XXIst century that should lead to a deep revision of the RRT concept. Optimal treatment of ESRD patients rely clearly on several options that may be used sequentially to solve specific complications and should be part of a complete management program including renal transplantation in patient non contraindicated.