Transfusion reactions are common occurrences, and clinicians who order or transfuse blood components need to be able to recognize adverse sequelae of transfusion. The differential diagnosis of any untoward clinical event should always consider adverse sequelae of transfusion, even when transfusion occurred weeks earlier. There is no pathognomonic sign or symptom that differentiates a transfusion reaction from other potential medical problems, so vigilance is required during and after transfusion when a patient presents with a change in clinical status. This review covers the presentation, mechanisms, and management of transfusion reactions that are commonly encountered, and those that can be life-threatening.