Transfusion-related acute lung injury (TRALI) is the major cause of transfusion related morbidity and mortality, world wide. Efforts to reduce or eliminate this serious complication of blood transfusion are hampered by an incomplete understanding of its pathogenesis. Currently, TRALI is thought to be mediated by donor alloantibodies directed against host leukocytes or the result of 2 distinct clinical events. For both proposed mechanisms, the neutrophil is the key effector cell. This article reviews TRALI pathophysiology, explores the role of the neutrophil, details practical information for appropriate diagnosis and promotes further studies into the pathogenesis of TRALI.