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The safety of allogeneic blood and blood products in relation to infection risk is paramount, even though absolute safety is an ideal that clearly cannot be attained. In countries with developed healthcare systems and with effective and well-managed national transfusion services, any residual infection risk is generally much lower than the risk of non-infectious adverse events. The number of infectious agents known to be transmitted by transfusion is not insignificant, but at the same time only a proportion of these present a significant universal threat. It is therefore important to understand and attempt to quantify the residual infectious risks associated with transfusion. These risks generally fall into two categories: the risk of infection because of the failure to identify infection in a donation from a recently infected donor and the risk of infection from a ‘new’ infectious agent or from one that donations are not routinely screened for. Both of these scenarios are ‘real’ in the sense that these are the threats faced every day by transfusion services. The mitigation of such threats is by ensuring that there are effective donor screening and deferral procedures in place, that the screening performed is carried out to the highest possible standards in terms of sensitivity and reliability, and finally that the transfusion service actively monitors ‘new’ or emerging infectious threats so that action can be taken if the safety of the blood supply is likely to be compromised, as well as maintaining hemovigilance of adverse events in recipients of transfusions.