The objective of this review is to present the two-event model of transfusion-related acute lung injury (TRALI), a life-threatening complication of transfusions that has been the most common cause of transfusion-related death over the past 2 yrs in the United States. The two-event model of TRALI, which is identical to the pathogenesis of the acute respiratory distress syndrome (ARDS), is reviewed and contrasted to antibody-mediated TRALI. Laboratory studies, both in vitro and in vivo, are discussed as well as human studies of TRALI. Methods to avoid patient exposure to blood components that may cause TRALI are also discussed.