A substantial body of animal data indicates that transmissible spongiform encephalopathies (TSEs) are transmitted through blood. These data have been augmented in the past year by reports that two recipients of red cells from donors with variant Creutzfeldt–Jakob disease (vCJD) in the United Kingdom have acquired this infection. Most of the blood donations collected in countries affected by bovine spongiform encephalopathy (BSE) and vCJD also contribute plasma to fractionation pools. Thus, a number of batches of fractionated products have included plasma from donors who developed vCJD. On the basis of public health strategies influenced, in part, by risk assessments, the UK and the French authorities have instituted measures for recalling products and informing patients of the estimated risks. It is therefore relevant to review the principles used by authorities in generating risk assessments for the transmission of TSEs by blood and blood products. While the general principles are fairly straightforward, the final assessments are very dependent on the magnitude of several key parameters, which are, largely, still unknown. A critical determinant of final product risk is the extent to which the plasma fractionation process will contribute to eliminating the infectious prion agent. Therefore, regulatory and industry measures to characterize fractionation processes for their capacity to eliminate prions are to be strongly encouraged. In the interim, an understanding of the principles used to generate risk assessments should contribute to an enhanced ability to address this threat to patient safety. Authorities should recognize that adequate communication is an integral part of good risk-management practices.