Malaria remains a rare but serious complication of transfusion because of the asymptomatic persistence of parasites in some donors. In nonendemic countries, the predominant strategy of deferral or cellular component discard from "risk" donors is effective in minimizing the incidence but is wasteful. In endemic countries where recipients are commonly immune, transfusion strategies focus on chemoprophylaxis for the donor and recipient or ensure that blood collected in highly endemic regions is not transfused to patients from areas of low endemicity. Donors implicated in transfusion-transmitted malaria are predominantly "semi-immune" with very low parasite loads. Their detection by even the most sensitive antigen or polymerase chain reaction (PCR) assays cannot be guaranteed and, in a number of cases, is unlikely because the infectious dose is estimated to be 1 to 10 parasites in a unit of blood. Retrospective analysis of implicated donors has confirmed the presence of high titer antibodies in such individuals. In regions of low immunity, serological assays offer an efficient method to identify such infectious donors. The recent development of enzyme immunoassays (EIAs) with improved sensitivity to Plasmodium falciparum and Plasmodium vivax , the predominant transfusion threats, has heightened the appeal of serological testing. Although universal serological screening in nonendemic regions is not cost-effective, targeted screening of donors identified at risk by travel-based questioning can significantly reduce wastage through reinstatement. Importantly, transfusion safety does not appear to be compromised by this approach as evidenced by the lack of a documented transmission in France between 1983 and September 2002, where such a strategy has been used since 1976. The development of automated protein microarray-based technology has the potential to further enhance antibody/antigen sensitivity; however, its application to donor screening is likely to be some years off. There is also the potential that pathogen inactivation techniques currently under development to address the bacterial contamination of blood components may also be effective against malaria parasites to make malarial testing redundant or at least reduce its cost/benefit ratio. Nonetheless, there are still significant problems to be solved in respect of validating and licensing these systems. Assuming that they are successfully marketed, their high cost may also impact their cost-effectiveness in comparison with targeted malaria testing strategies already in place in some jurisdictions.