Liver transplantation has become the accepted method of treatment for children with end-stage liver disease. Combining new methods of immunosuppression, modifications in surgical technique, improved anesthetic management, organ availability, and identification and treatment of postoperative complications, survival rates have reached 80% to 90% in many centers performing pediatric liver transplants. With the improvement in survival rates, indications for liver transplantation in children have broadened; however, the availability of organs suitable for children is still extremely limited. Although pediatric cases only represent approximately 10% of the total patients on the waiting list, the number of deaths on the waiting list increased from 196 in 1988 to 1753 in 1999. The recent development of surgical procedures that enable the use of cut down "reduced" livers, split liver grafts (splitting a cadaveric liver for 2 different recipients), and living related donors, are creating new options for the long list of children waiting for hepatic transplants. In light of the increasing incidence of liver disease and continuing shortage of donor organs, cell-based therapies are getting attention as promising treatments for liver failure. These include: isolated cell transplantation, tissue engineering of implantable constructs, transgenic xenotransplantation, and extracorporeal bioartificial liver devices. Hepatocyte transplantation aims to correct inborn errors or acquired liver function defects by supplying metabolically active cells to the diseased liver. Experimentally, hepatocytes can be successfully isolated by collagenase digestion of the liver. Cells can then be transplanted in the spleen or the liver via the portal vein or hepatic artery. In both sites, cells engraft and become metabolically active, can synthesize albumin, or correct inborn errors of metabolism. They have been shown to prolong survival in models of fulminant liver failure, and so far have been shown to bring partial metabolic control in Crigler-Najjar disease type I and Refsum disease. Extracorporeal support for patients with liver failure has been attempted for over 40 years. Various nonbiological approaches have met with limited success, presumably because of the role of synthetic and metabolic functions of the liver that are inadequately replaced in these systems. Bioartificial devices typically incorporate isolated cells into bioreactors to simultaneously promote cell survival and function as well as provide for the level of transport seen in vivo. While the safety of bioartificial liver devices has been established, there are no uniform standards of efficacy that may vary with the etiology of the liver failure. Consensus is needed in clinical trial design, including choice of the end points, use of controls, and indications for enrollment. Also, a better understanding of the interplay between liver regeneration and bioartificial liver support therapy will be critical to optimizing the implementation of this modality. Pediatric liver transplantation is a challenging and rewarding field with continued improvement in patient and graft survival. A multidisciplinary team approach coupled with improvement in organ availability, immunosuppression, and peri-operative management has had a dramatic impact on survival. The increasing incidence of liver disease and continuing shortage of donor organs has led to the development of new therapies using cell-based therapies as an alternative to transplantation. The procedure is less radical, less invasive, potentially less expensive, and fully reversible. It may, to a certain extent, alleviate the problem of organ shortage. Despite these advances, transplantation remains a costly procedure and patients still require lifelong immunosuppressive therapy subjecting them to potential side effects and infections. In some children with liver disease, transplantation is the only alternative, whereas in others the risks and benefits must be considered relative to other treatment options.