Historically, the transfusion reaction evaluation is a Blood Bank protocol for determining the presence of immune-mediated hemolysis. It calls for an initial workup, and if no evidence of certain pre-set criteria exists, the investigation ends. In this seminar, the speakers discuss inflammatory responses, likely non-hemolytic, that are life-threatening when not recognized and managed. The lecturer will address signs and symptoms of pulmonary reactions to blood transfusions that may be neither immediate nor classic signs of reactions to transfusion, and therefore are unrecognized, unreported and not managed. The speakers will discuss clinical and laboratory investigations that not only diagnose transfusion-associated acute lung injury (TRALI) but also differentiate this diagnosis from that of transfusion-associated circulatory overload (TACO) or other pulmonary episodes. This interactive seminar will review radiologic and laboratory testing used in the clinical context. The speakers will discuss strategies for minimizing transfusion risk by proper management of at-risk donors, thereby complying with AABB guidances.