Patients with small-for-size syndrome (SFSS) and acute liver failure share some important clinical features that are paralleled by common approaches to their intensive care unit management. Both are characterized by a period of acute hepatic insufficiency, with clinical features reflecting the impairment of metabolic and immunologic function that results. The basic principles of management of the two conditions remain essentially the same: to support hepatic regeneration, to anticipate and prevent the development of complications, and to identify patients unlikely to survive early in their clinical course so that retransplantation may be considered. Many treatments are available in the intensive care unit to overcome biochemical and metabolic disturbances in acute liver failure. Optimal pharmacologic management of SFSS complicated by portal hypertension and variceal hemorrhage is currently uncertain. Extracorporeal liver support has several theoretical attractions in the critically ill patient with SFSS, through its ability by removal of hepatotoxins to provide an environment more conducive to hepatic regeneration and recovery, or to support and bridge the patient to transplantation. The molecular adsorbent recycling system has been proposed to remove both water-soluble and protein-bound toxins. This system is particularly attractive in the treatment of SFSS, however, despite its current clinical application, there are presently limited published data to support its use.