INTRODUCTION more expediently, potentially increasing availability The rational for allogeneic transplantation as therapy for inherited metabolic disease was provided by the fundamentally important work done by Neufeld’s group over 40 years ago, confirming that normal cells could “cross-correct” cells with storage diseases such as Hurler syndrome. Initial reports in the early 1980s confirmed that these patients could be transplanted, resulting in improvement in visceral disease in patients with mucopolysaccharide accumulation. Later investigations suggested that transplantation arrested neurologic deterioration in some disorders, such as Hurler syndrome (mucopolysaccharidosis type IH [MPS IH]), but is less effective in achieving stabilization of cognitive function in MPS II (Hunter) and MPS III (Sanfilippo). It is thought that the engraftment of donor-derived microglia results in the delivery of enzyme in the central nervous system, but the reasons transplantation is more successful for MPS IH than MPS II or MPS III remain elusive. Transplantation was also tested as therapy for lysosomal leukodystrophies, including Krabbe (globoid cell leukodystrophy, or GLD) and metachromatic leukodystrophy (MLD). ALthough isolated reports of success in disease stabilization for GLD and MLD exist, due to heterogeneity of disease phenotypes and degree of disease advancement at the time of transplantation, analysis of these outcomes are difficult, and there are no large multicenter reports of outcomes. Reports of success in the use of transplantation for adrenoleukodystrophy (ALD) were first published in the 1990s. Because ALD is a peroxisomal disorder, the biology by which transplantation exerts its beneficial effects is distinct from that of GLD and MLD. Other rare inherited metabolic diseases, including osteopetrosis, mannosidosis, MaroteauxLamy syndrome (MPS VI), and Wolman disease, for instance, have also been reported to respond to transplantation. New developments have affected approaches to transplantation for these disorders. The availability of enzyme replacement therapy (ERT) has provided the opportunity to explore combination therapy in disorders such as Hurler syndrome, whereas in other diseases, such as MaroteauxLamy syndrome, ERT has essentially replaced transplantation as standard therapy. In addition, cord blood (CB) transplantation has allowed patients to move to transplant