Blood purification by means of plasmapheresis has been known since the 1950s. Plasmapheresis first separates plasma from the blood's cell component; in the classical plasma exchange modality, the patient's plasma is then replaced with fresh frozen plasma from a donor. This procedure is still current in different fields of medicine, as there are hematological (thrombotic thrombocytopenic purpura, Waldenström's disease), neurological (Guillain-Barre' syndrome, myasthenia gravis) and toxicological indications (several forms of mushroom poisoning, tricyclic antidepressants, transfusional reactions), as well as nephrological indications (Goodpasture's syndrome, ANCA-associated vasculitis, myeloma) for its use. Many of these diseases are encountered in the intensive care setting due to the organ dysfunction they may cause. In recent years, purification procedures have been developed that avoid the replacement of plasma by purifying plasma directly. Once treated, the plasma can be returned to the patient, thereby avoiding the loss of factors like vitamins, coagulation proteins, and antibodies and at the same time reducing the possible risk of infection. The technological prerequisite is the use of cartridges containing absorbent material (resins) on which the plasma obtained from the plasma separation is perfused. The physicochemical characteristics of the resins allow them to trap large-sized or protein-bound solutes. Such procedures have found particular application in two fields typically related to intensive care: liver failure and sepsis. The future of plasmapheresis seems oriented towards increasingly selective treatments capable of removing only those molecules that are the cause or associated cause of the damage.