There is continuing controversy over the role of extracorporeal blood purification therapies in the treatment of septic patients. There is also controversy over whether the immune system as a target for manipulation in severe sepsis or septic shock. It has been argued that the immune system is too complex for successful manipulation and that interventions aimed at attenuating the blood levels of single or multiple mediators are pointless. Furthermore, several investigators have pointed out that the timing of such interventions is often too late and that ICU conditions such as septic shock and the multiorgan dysfunction syndrome contain too many confounding variables for a single intervention to work. Therapeutic nihilism has set in on the ability of a single intervention to show any effect in the ICU environment and, in particular, on the ability of immune system targeting to yield clinically meaningful results. Extracorporeal blood purification therapies have been viewed as an approach to sepsis that is underpinned by a misguided rationale and doomed to failure. However, such conclusions are premature because as the sophistication of these therapies evolves and their rationale becomes more refined, it can be seen that the outcome of critically ill patients can be modifled by specific therapeutic interventions. (C) 2000 Lippincott Williams and Wilkins, Inc.