Sickle cell disease (SCD) is one of the most common genetic disorders in the United States. Once a fatal disease of childhood, the majority of patients born with SCD who live in a developed country will survive to adulthood (albeit with slightly shortened life spans). Despite numerous novel therapeutic advancements in recent years that serve to mitigate the symptoms associated with SCD, the only cure for SCD is a hematopoietic stem cell transplant. The overall survival for patients with a matched sibling donor transplant is greater than 90%. However, fewer than 20% of patients with SCD in the US have a 12/12 human leukocyte antigen (HLA) matched sibling donor. In contrast, most patients have at least one HLA haploidentical first-degree relative, which expands the donor pool for patients who have diseases amenable to stem cell transplantation such as SCD. [Pediatr Ann. 2022;51(1):e34-e39.].