Transmissible spongiform encephalopathies (TSEs) are a family of rare, slowly progressive, and universally fatal neurodegenerative syndromes affecting animals and humans. Until recently, TSEs were of little interest to pediatricians. However, since the outbreak in adolescents and the association of TSEs with new-variant Creutzfeldt-Jakob disease (nvCJD), interest among pediatricians and the general public has increased. Even before bovine spongiform encephalopathy and nvCJD were linked, the recognition that iatrogenic Creutzfeldt-Jakob disease (CJD) had been acquired from administration of cadaveric human growth and gonadotropic hormones and from corneal and dura mater transplants prompted medical vigilance. Furthermore, recent concern about the potential for transmission of CJD by blood and blood products has raised awareness among public health and regulatory agencies, pediatricians, and the public, although no epidemiologic data support this concern. Because of worldwide concern (although no cases have been reported in North America), this review focuses on the potential impact of TSEs, particularly CJD and nvCJD, on the pediatric population.