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Red cell transfusions represent the main treatment of acute blood loss anemia; however, there are patients who are unable or refuse to receive blood products. Further, in all patients, it is essential to only transfuse when the benefits of transfusion outweigh the risks. In those patients who are unable to receive a blood transfusion, it is important to have a multidisciplinary treatment plan. Further, for those patients requiring surgery, it is important to consider the pre-, intra-, and postoperative periods. Many of the principles and strategies outlined in this article can be applied to patients across clinical contexts and are not exclusive to the surgical setting. Before any planned surgery or intervention, all patients should be screened for anemia at least 6 weeks prior to their anticipated surgical or delivery date. Anemia should be corrected, and the patient's bleeding history should be documented. Strategies to reduce blood loss intraoperatively should be discussed with the surgical and anesthetic team. A plan for emergency management of bleeding and treatment to reduce risk, both intraoperatively and postoperatively, should be developed. The patient's decisions about which, if any, blood products or fractions are acceptable should be documented. Intraoperatively, surgical and anesthetic techniques to minimize bleeding should be used along with appropriate medications. Postoperatively, considerations include the minimization of blood sampling, ongoing support of the patient's hemoglobin mass, and optimization of the physiologic tolerance of anemia. Options exist to allow for the safe and effective management of patients who refuse or are unable to receive blood transfusions. It is essential to have clear communication and documentation of the goals of therapy as well as acceptable interventions. The involvement of a multidisciplinary team to manage the patient is essential.