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Restrictive blood transfusion practice has modified the indications for blood transfusion. There is still a need for succinct definition of transfusion thresholds in different situations, based on physiological argument balancing the mechanisms by which blood is potentially beneficial against the deleterious effects of transfusion, whether known, speculative or unknown. The latter still need identification. The key physiological benefit is through oxygen delivery and thereby the provision of a margin of safety in tissue oxygenation. This can be achieved by a range of methods that safeguard blood volume, conserve blood or increase hemoglobin as well as by transfusion, and in many situations conservation methods can or could now preclude transfusion. There are still acute and less controlled or controllable situations where conservation methods are difficult to implement or may need to be complemented by transfusion. These are the indications that still need clarification. Difficult and confusing areas of practice include the management of patients with ischemic heart disease. This is a potential driver for transfusion to prevent ischemia, but clarity of efficacy or detriment is elusive beyond acknowledging that both too high and too low hemoglobin values are detrimental. The issue in all clinical situations, whether acute or chronic, is to continue to reevaluate the safety of current thresholds. This will help limit blood usage and ensure that blood is used when necessary but not otherwise.