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Transfusion-related acute lung injury (TRALI) is a rare but serious syndrome characterized by sudden acute respiratory distress following transfusion. It is defined as new, acute respiratory distress during or within six hours of blood component (i.e., red blood cells, plasma, platelets) or blood product (i.e., plasma protein product) administration in the absence of temporally-associated risk factors for acute respiratory distress syndrome (ARDS). All plasma-containing blood components and plasma protein products have been implicated in TRALI, including rare reports with intravenous immunoglobulin (IVIg) and cryoprecipitate. Despite the very small amount of plasma contained in red blood cells, this component is associated with the largest number of reported cases of TRALI. TRALI is thought to be caused by activation of recipient neutrophils by donor-derived antibodies targeting human leukocyte antigens (HLA) or human neutrophil antigens (HNA). Non-antibody-mediated cases also occur and may be mediated by biologic response modifiers present in the transfused blood component or plasma protein product, along with recipient factors.