New-variant Creutzfeldt-Jakob disease (nvCJD) was first described in the UK in 1996 and is thought to be related to the consumption of cattle suffering from bovine spongiform encephalopathy. Although only 29 cases have been confirmed to date, it is too early to predict the number of people who may currently be incubating the disease. Past experience suggests that sporadic CJD is rarely, if ever, spread by blood transfusion. However, it is unclear whether nvCJD may be transmissible by this route and if so, how easily. Assessing the potential risk of transmission of nvCJD by blood transfusion and evaluating the likely efficacy of proposed strategies to reduce this risk is, therefore, very difficult. This article summarizes the spectrum of transmissible spongiform encephalopathies in animals and man, the molecular and cellular biology of the prion protein and the continuing debate as to the nature of the infectious agent. The distribution of normal prion protein expression, the results of experimental transmission studies and the case reports and clinical studies on CJD transmission are reviewed. Finally, the extent of current knowledge and the potential utility of proposed strategies to reduce the risk of nvCJD transmission by blood transfusion are discussed.