Hematopoietic cell transplantation (HCT) is a treatment with curative potential for sickle cell disease (SCD). The experience of HCT for persons with β-thalassemia major has been successfully extended to SCD. Currently, the event-free survival rate after allogeneic-matched sibling HCT for SCD is 82%. However, short-term and long-term transplant-related complications remain substantial barriers to HCT, particularly in older patients with life-long complications of SCD. Novel conditioning regimens that minimize transplant-associated toxicity have been developed and show promise for wider application of HCT. Alternative stem cell sources may also expand the availability of HCT for selected patients with SCD.