Recognizing and investigating acute reactions to transfusion is important to ensure optimal patient outcomes and safety of the blood supply; hence, it is important for physicians and health care professionals to understand the types of reactions that can occur, including their pathophysiology, aetiology, clinical presentation, differential diagnosis and investigation and management. Even with an understanding of these events, identifying the type of reaction can be challenging as most clinical signs and symptoms are not specific to one type of reaction. Consideration of other variables such as patient history, medications, the type and volume of product being transfused and the presence or absence of fever will provide useful pieces of the puzzle to assist in arriving at a definitive diagnosis. A practice approach for the investigation, reporting and follow‐up of acute reactions to transfused blood components is presented.