The process of curing a patient by removing his illness by extracting blood is a very old one. Many years ago, phlebotomy was practiced to cure illness. Now, this old process, placed on a rational basis with therapeutic apheresis (TA), is being followed in clinical practice. Therapeutic plasma exchange (TPE) with hollow fiber modules has been used in different severe diseases for more than 40 years. Based on many years of experience with the extracorporeal circulation in end-stage renal disease, the authors herein give an overview of TA in immunological diseases, especially in hematologic, autoimmune and dermatologic diseases. Updated information on immunology and molecular biology of different immunological diseases is discussed in relation to the rationale for apheresis therapy and its place in combination with other modern therapies. With the introduction of novel and effective biologic agents, TA is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved in recent years, due in part to very aggressive therapy schemes. For the immunological diseases that can be treated with TA, the guidelines of the German Working Group of Clinical Nephrology and of the Apheresis Applications Committee of the American Society for Apheresis are cited. TA has been shown to effectively remove the autoantibodies from blood and lead to rapid clinical improvement.