Optimal use of blood is defined in this manual as ‘The safe, clinically effective and effcient use of donated human blood.” However, for many of the familiar and widely accepted indications for transfusion it is a fact that there is surprisingly little high quality evidence to establish the effectiveness of transfusion therapy. As a result, clinical transfusion guidelines must often be based on inadequate information. Information in this chapter about the quality and grading of evidence for clinical practice guidelines has been drawn from the German Guidelines for Therapy with Blood Components and Plasma Derivatives (2009). Another useful sources is the database of systematic reviews at the website www.transfusionguidelines.org.uk (go to Evidence Library).