To review treatment approaches for temporary liver support of patients with acute liver failure (ALF). STUDY A MEDLINE: search of English language reports published between 1960 and 1999 and a manual search of bibliographies of relevant papers were performed. Studies of humans in whom non-orthotopic liver transplant (OLT)-based approaches were used were reviewed, including case reports, case series, review articles describing unpublished cases, and controlled trials. Relevant clinical information was extracted with emphasis on improvement in liver function, successful bridging to OLT, recovery without OLT, and death. There was a lack of more than one controlled trial for each therapy, and most case reports were anecdotal in nature; therefore, no statistical analysis was attempted. Predefined outcomes from individual patients were synthesized collectively into tables. Both cell-based and non-cell-based therapies for ALF appear promising. Preliminary experience has established the safety of these approaches, but current data are inadequate to evaluate efficacy. Routine use of artificial liver support systems cannot be recommended at this time. However, the established safety of cell- and non-cell-based liver support devices warrants additional prospective (Phase III) controlled trials among patients with ALF. We suggest an algorithm for management of patients with ALF that incorporates recent data.