West Nile virus (WNV) entered North America in 1999 and in 2002 was shown to be transfusion transmitted. With competent mosquito and bird vectors throughout the United States and Canada, WNV clinical disease continues at epidemic proportions. Due to these facts, blood donor screening was implemented prior to the 2003 mosquito season and occurs using a variety of strategies. A combination of minipool (MP) nucleic acid amplification testing (NAT) during the " non-season, " coupled with the conversion to the more sensitive individual donation (ID) NAT in epidemic locations during epidemic times, has been successful in detecting approximately 1500 infected blood donors. Assuming that each donation was infectious and manufactured into 1.45 blood components, testing has therefore prevented close to 2200 recipient infections and potential clinical disease. During this same time, transfusion transmission has occurred from seven MP NAT nonreactive/ID NAT reactive units (6 in 2003 and 1 in 2004), or a total of 30 transfusion transmitted cases since WNV has been identified in North America. Because WNV occurs in infected blood donors at low concentrations (i.e., lower viral loads than HIV or HCV with the highest viral load of 580,000 copies/mL observed in a blood donor), a trigger strategy that is used in most of the US consisting of two NAT reactive donations detected by MP NAT and a frequency of 1 :1000 or greater has been developed. Since the full implementation of the MP to ID NAT trigger strategy, there have been no documented WNV transfusion transmissions. Because WNV is an acute infection that only occurs seasonally, other strategies have been proposed, such as seasonal testing, which has been implemented successfully in Canada (Quebec), coupled with a screening question used in the " non-season " of whether the donor has been in the US during the past 56 days; if so, WNV NAT is performed. WNV is an example of an emergent agent in which a rapid series of interventions has been successful in controlling transmission through blood transfusion.