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The precautionary principle has emerged as an important new paradigm influencing decision making in the blood system. The principle has influenced decision making in several nations leading to the institution of policies to protect their blood supplies form variant Creutzfeldt-Jakob disease (vCJD). Increasingly evidence has emerged to support the institution of these policies, which were introduced in advance of clear evidence of risk. These vCJD decisions serve as an example of the successful application of precaution and provide lesions as to how the principle should be applied in future transfusion safety decisions.