Despite the increased safety of blood achieved through continued improvements in donor testing, concern remains about the safety of blood components. Transfusion of cellular components has been implicated in transmission of viral, bacterial, and protozoan diseases. While it is commonly recognized that hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), and the retroviruses, such as human immunodeficiency virus (HIV) and the human lymphotrophic viruses (HTLV) can be transmitted through cellular components, other pathogens are emerging as potentially significant transfusion-associated infectious agents. For example, transmission of protozoan infections due to trypanosomes and babesia have been reported. In addition to viral and protozoal infectious agents, bacterial contamination of platelet concentrates continues to be reported; and may be an under reported transfusion complication. More importantly, new infectious agents may periodically enter the donor population before they can be definitively identified and tested for to maintain consistent safety of the blood supply. The paradigm for this possibility is the HIV pandemic which erupted in 1979. During the past decade a number of methods to inactivate infectious pathogens in blood components, including platelets, have been developed. This technology is now entering the clinical trial phase.