Renal replacement therapy (RRT) has evolved from the concept that we need to treat the dysfunction of a single organ (the kidney). As intensive care units have become more and more complex, it has become clear that the majority of patients with acute renal failure often have dysfunction of several other organs. In order to facilitate single organ support in this setting, continuous renal replacement therapy (CRRT) techniques have been developed. However, CRRT has opened the door to the concept that targeting renal support as the only goal of extracorporeal blood purification may be a simplistic view of our therapeutic aims. In this article we argue that it is now time to move from the simple goal of achieving adequate renal support. The proper goal of extracorporeal blood purification in ICU should be multi-organ support therapy (MOST). We explain why MOST represents the most logical future conceptual and practical evolution of CRRT and illustrates the biological rationale, supplying animal and clinical evidence that confirms the need to move rapidly in this direction theoretically, practically and technologically.