Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. TRALI presents as acute lung injury (ALI) within 6 hours after blood product transfusion. Diagnosing TRALI requires a high index of suspicion, and the exclusion of circulatory overload or other causes of ALI. The pathophysiology of TRALI is incompletely understood, but in part involves transfusion of certain anti-neutrophil antibodies, anti-HLA antibodies, or other bioactive substances, into susceptible recipients. Recent studies have identified both recipient and transfusion risk factors for the development of TRALI. This article describes these TRALI risk factors, as well as diagnosis, treatment and prevention strategies.