As both iatrogenic and experimental transmission of Creutzfeldt-Jakob disease (CJD) have been demonstrated, potential blood transfusion-related CJD through blood component contamination is not unlikely. Recent studies also suggest that B lymphocytes would play a crucial role in the disease pathogenesis. However, to date, there is no epidemiological evidence suggesting that classical transmission of CJD would involve B lymphocytes. To reduce the theoretical risk of such transmission and as no biological marker of the disease is currently available, at-risk blood donors are excluded and leukocyte depletion has been introduced. Furthermore, the recent discovery of a new variant of the disease (nwCJD) which is caused by the bovine agent and has typical tropism for lymphoreticular tissues should lead to close surveillance.