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The use of umbilical cord blood (UCB) as a stem cell donor source has dramatically increased over the last 2 decades. Patients undergoing UCB transplantation share medical management issues with patients receiving a hematopoietic stem cell transplantion using adult donor sources (peripheral blood stem cells or bone marrow stem cells) and may also have more complex medical issues that appear to be related to delayed immune recovery from UCB-derived stem cells. The interface with critical care providers is likely to occur in the transplant and posttransplant setting. Patients may experience UCB infusion reactions that range from mild to rarely severe. Following transplant, patients are transfusion dependent for long periods due to the prolonged engraftment of UCB cells. They are at high risk of infection, particularly viral. Once engrafted, UCB transplant patients have a lower rate of graft versus host disease compared to other donor sources. Some of the other complications that are seen in patients undergoing UCB transplant are posttransplant lymphoproliferative disease, diffuse alveolar hemorrhage, and posterior reversible encephalopathy will also be discussed.