Transmissible spongiform encephalopathies (TSE) are rare lethal diseases induced in humans and animals by unconventional agents (TSA) named also prions or virinos. TSA/prions have unconventional properties; in particular, they resist to almost all the chemical and physical processes which inactivate conventional viruses. Natural history of TSE indicates that organs are infectious a long time before the appearance of the clinical symptoms. The only specific marker of the TSA infections is the post-translational accumulation of the host encoded protein PrP (Prion Protein). Iatrogenic Creutzfeldt-Jakob disease (CJD) cases have been described after neurosurgery, treatment with pituitary derived hormones, and cornea and dura mater grafting. TSA associated infectivity is depending upon the nature of the organ in a given infected individual: central nervous system has the highest infectivity, spleen and lymph nodes a medium infectivity, and organs like bone or skin do not harbor any detectable infectious particle. Therefore, donors with neurologic history must be excluded and treatment with pituitary derived hormones should be considered as potentially infected with TSA, and excluded.