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Sickle cell disease is a congenital haemoglobinopathy with a high incidence of perioperative complications. Traditional anaesthetic management, based largely on extrapolation from biochemical models, has emphasized avoidance of red cell sickling to prevent exacerbations of the disease. This historical review outlines the evolution of the traditional approach to sickle cell pathology, assesses the validity of this model, describes the emergence of the concept of the disease as one defined by chronic inflammatory vascular damage, and outlines the practical implications of this new approach.