Patients and families often request that their potential perioperative blood needs be met with autologous or directed donations. Autologous transfusions can occur in a variety of ways, including self-donation prior to a procedure (preoperative autologous donation, PAD), during surgery using hemodilution (acute normovolemic hemodilution, ANH), through cell salvage during or after surgery, or in the peripartum period (i.e., placental harvest or delayed cord clamping). A directed donation originates from an individual that a potential blood recipient chooses, and that person is typically an acquaintance or family member. In the United States (US), the rate of designated donor transfusions and PAD has decreased appreciably over the past several decades. PAD is only suited for planned surgeries with a likelihood of significant blood loss, partly because a significant percentage of units are unused and go to waste. The main indications for PAD include elective surgeries where significant blood loss is anticipated in the face of a rare blood type or in patients with multiple alloantibodies. PAD in children entails special considerations, and there are no well-established guidelines addressing pediatric PAD. PAD is a controversial alternative for cancer patients. However, national organizations with blood donation oversight allow some cancer patients to donate their blood under certain conditions. Although requests remain relatively high, especially for children, many blood centers recommend against directed donations outside of exceptional circumstances. The most common indication for receiving a directed donation is when the patient has multiple alloantibodies to red blood cell (RBC) antigens that exist in high frequency in the population, and the only blood resource available is a family member or other specific person. Both PAD and directed donations are subject to standard processing requirements, including a physician’s order, approval by both the referring physician and the blood center, and informed consent. Most blood centers require that the blood be donated no less than 72 h before the intended surgery. Concerns about designated donor transfusions include transfusion-associated graft versus host disease (TA-GVHD), a potentially fatal condition, and recipient human lymphocyte antigen (HLA) sensitization, which may limit future organ transplants from related donors.