Transfusion-related acute lung injury (TRALI) remains the deadliest complication of transfusion. Consensus definitions of TRALI have been developed but remain controversial. Recent evidence supports a strong relationship between blood transfusion and the development of acute lung injury in the critically ill and trauma population. Plasma and platelet transfusions have been the most commonly implicated blood products. The 'two hit' model may best explain the immune and nonimmune pathogenesis of TRALI. Current treatment remains largely supportive; effective measures for decreasing the incidence of TRALI include the use of predominantly male plasma and apheresis platelets. Greater understanding of the blood component and patient risk factors for TRALI will hopefully lead to novel treatment and preventive strategies for reducing the risk of this life-threatening syndrome.