The transmissible spongiform encephalopathies (TSE) represent a group of neurodegenerative diseases with lethal outcome. They include Creutzfeldt-Jakob disease (CJD) and kuru, among others in humans, scrapie in sheep and spongiform encephalopathy in cattle (bovine spongiform encephalopathy: BSE). Some are autosomal dominant disorders like CJD, Gerstmann-Straüssler-Scheinker disease (GSS), with point mutation of the prion protein gene. Most of these diseases are idiopathic rather than sporadic, latrogenic CJD could be obtained by central inoculation (neurosurgical instruments or dura mater grafts) or by peripheral inoculation (pituitary hormone therapy). A new variant clinicopathological type of CJD (nvCJD) has been reported. The nvCJD has strain characteristics distinct from other types of CJD, close to those of BSE transmitted (studies with intracerebral inoculation), consistent with BSE being the source of this new disease. All of these spongiform encephalopathies (SE) are characterized by spongiform degeneration of the brain, reactive gliosis in the cortical and subcortical gray matter, neuronal loss and presence of the abnormal isoform of the cellular prion protein (PrPc). In prion disease, PrPc undergoes conformational changes involving a shift from alpha-helix to beta-sheet structure. These neurologic lesions are characterized by major variations from case to case. Neuropathological studies in sporadic CDJ have emphasized phenotypic variations. Clinical presentation with a wide spectrum of manifestations is a rapidly progressive dementia, associated with myoclonus or akinetic mutism and cortical blindness. The clinical course is atypical and when the characteristic triphasic abnormal EEG of CJD is absent, there is an urgent need for a premortem diagnostic test. Histopathological examination of a brain biopsy carries a risk of major morbidity and may miss the site of disease. The 14-3-3 immunoassay of cerebrospinal fluid strongly supports a diagnosis of CJD. Western blot analysis of human tonsil biopsy may allow an early or preclinical diagnosis. It has been suggested that CJD might be transmitted by blood products derived from patients with CJD during the prodromal stage, although CJD linked aetiologically to blood transfusion has not been demonstrated. In animal studies, intracerebral inoculation of infected cells has been associated with development of disease, but never after peripheral inoculation into the blood stream. For the most part of conformational changes of PrPc, the remarkable resistance of the infectious agent (PrP alone or combined) to ordinary sterilising procedures is a major problem. Because of this resistance, current recommendations are to recognize patients at risks and to use disposable medical devices. This is particularly true in anaesthesia during endotracheal intubation, spinal anaesthesia, and to a lesser extent with peripheral nerve blocks. All instruments used for patients with CJD must be destroyed. The economic consequences of these measures have highlighted the essential importance of an early diagnosis.