Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) represents the only curative treatment for sickle cell disease (SCD), being successful in around 85–90% of patients. Mortality and long‐term morbidity (including infertility, gonadal failure, and chronic graft‐vs.‐host disease) associated with conventional approaches curtail the number of patients who undergo allo‐HSCT. Recently, it has been demonstrated that cord blood is as effective as and possibly safer than bone marrow in pediatric patients with SCD. Likewise, transplant strategies based on the use of reduced‐intensity regimens and the induction of mixed chimerism have been explored to decrease allo‐HSCT short‐ and long‐term complications. Pediatr Blood Cancer 2012;59:372–376. © 2012 Wiley Periodicals, Inc.