Transfusion of blood and blood components has been a routine practice for more than half a century. The rationale supporting this practice is that replacement of blood loss should be beneficial for the patient. This assumption has constituted the underpinning of transfusion medicine for many decades. Only over the past 20 years, we have seen a more concerted effort to answer very basic questions regarding the value of transfusion therapy. An assessment of the value of transfusion based on well-designed and appropriately powered randomized, controlled trials is the first step in optimizing transfusion practices. Systematic reviews provide the second step by building the knowledge base necessary to assess the impact of transfusion practice on patient outcomes. The third step is the development of clinical practice guidelines, and this occurs when systematic reviews are interpreted by individuals with expertise in transfusion medicine. Such guidelines are typically supported by professional organizations and/or health authorities. Implementation of clinical practice guidelines can be challenging, especially in an area as heterogeneous as transfusion medicine. However, clinical practice guidelines are necessary for the practice of evidence-based medicine, which optimizes patient care and improves patient outcomes. This review focuses on clinical practice guidelines for transfusion of three blood components: RBCs, platelets and plasma. In addition, we provide the approach used to implement clinical practice guidelines at our own institution.