Plasmapheresis has been applied over the last several decades as primary or adjunctive treatment for a number of primary renal diseases and systemic conditions with renal involvement. The present review discusses renal conditions for which plasmapheresis may be attempted with recommendations based on evidence from the literature. Other indications of special interest for renal physicians (e.g., sepsis and multiple organ failure, drug overdose, and poisoning) are also discussed. In addition, the present text reviews general apheresis principles, technical considerations for optimal plasmapheresis prescription, and possible complications of plasmapheresis. Knowledge of disease mechanisms and plasmapheresis principles is invaluable in applying a plasmapheresis treatment regimen appropriately.