Proper utilization of liver transplantation in the management of pediatric metabolic diseases requires a comprehensive understanding of both metabolic disease and the risk and benefits of transplantation. This brief review focuses on issues that pertain to the treatment of tyrosinemia type I, bile acid biosynthesis disorders, primary hyperoxaluria, Crigler-Najjar Type I, and mitochondrial diseases. These entities are used as prototypes to illustrate many of the principles that are applied in a more general sense to the management of metabolic diseases. The natural history of these disorders are considered in the context of the risks of liver transplantation. Indications, contraindications, and both current and future alternatives to transplantation, are considered.