Serious adverse effects of transfusion may be immunologically or non-immunologically mediated. Currently, bacterial contamination of blood products, particularly platelets, is one of the most significant causes of transfusion-related morbidity and mortality. Septic transfusion reactions can present with clinical symptoms similar to immune-mediated hemolytic transfusion reactions and transfusion-related acute lung injury. Extremely high fever and/or gastrointestinal symptoms, in a transfusion recipient, may be indicative of sepsis. The diagnosis is based upon culturing the same organism from both the patient and the transfused blood component. Numerous organisms have been implicated as the cause of septic transfusion reactions. Due to different storage conditions, gram negative organisms are more often isolated from red blood cell components; gram positive organisms are more often isolated from platelets. Prevention of septic transfusion reactions is primarily dependent on an adequate donor history and meticulous preparation of the donor phlebotomy site. Visual inspection of blood components prior to transfusion is also vital to preventing these reactions. Several methods of detection of bacterial contamination and inactivation of pathogens are currently under active investigation.