Treatment with blood and 'its substitutes is a common practice in surgical patients who bleed perioperatively; also, nonsurgical patients with chronic disease receive blood/blood components. However, some patients refuse blood because of personal or religious beliefs, like in the case of Jehovah's Witnesses. Those patients may accept different artificial substitutes of blood components as well as some surgical techniques, that decrease the risk of bleeding or the volume of blood lost. It is extremely important to inform the patients about the risk of losing blood without its replacement and to get an informed consent, as well as to document which treatments and/or procedures the patient consents to and which they do not. Such patients must be correctly prepared for the operation with hematologic optimization. All drugs that influence hemostasis must be stopped preoperatively. There have been several interventions/methods of decreasing the need for transfusion developed. All surgeons and anesthesiologists must be familiar with indications and appropriate use of blood and blood components and their alternatives, but close liaison with hematology specialists and their local blood sciences laboratory is encouraged. Based on the latest guidelines, there are many options of preoperative preparations and treatment, very important for the surgical and anesthesiology team, described in the manuscript.