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For more than two decades authorities have been calling for a major change in transfusion practice [1]. This is now even more urgent as new challenges continue to emerge. These include supply difficulties due to a diminishing donor pool and an increasing aging and consuming population, spiralling costs of blood and ongoing safety issues. Knowledge of transfusion limitations continues to grow, while a burgeoning literature demonstrates a strong dose-dependent relationship between transfusion and adverse patient outcomes [2, 3]. These factors combine to now make change vital [4].Historically, changing long-standing medical practice has been challenging– perhaps even more so in transfusion. Despite professional guidelines and educational initiatives, wide variations in transfusion practice exist between countries, institutions and even between individual clinicians within the same institution [5–8]. This suggests that much practice may be based on misconceptions, belief and habit rather than evidence. It is not the first time strongly entrenched belief has been an impediment to scientific progress. Edwin Hubble’s description of an expanding universe in 1929 has been hailed as one of the great intellectual revolutions of the twentieth century. However, it has been suggested that, because of knowledge of Newton’s law of gravity, an expanding universe could have been predicted over two hundred years earlier [9]. What slowed scientific progress? The widely held belief in a static universe prevailed. The belief was so strong at the time that in 1915 Einstein even modified his theory of relativity to accommodate it [9].A brief review of the history of transfusion provides some insights as to how a behavior-based practice developed in transfusion and therefore how change may be effected by a more patient-focused approach(Figure 1.1).