Sickle cell disease (SCD) is the most common inherited blood disease. Disease-modifying therapy and supportive care have improved the survival of children with SCD in the United States and Europe. Yet, adults with SCD continue to have high risks of morbidity and early death. Recently, 2 US Food and Drug Administration-approved genetic therapies offer the potential for a short-term decrease in acute vaso-occlusive pain events if not cure. Allogeneic hematopoietic cell transplantation (allo-HCT) is also curative but, until recently, was constrained by limited donor availability and the risks of graft-versus-host disease, graft rejection, and death. Importantly, recent advances have attenuated these barriers. Here, we discuss the current state of therapies with curative intent for SCD. Both genetic therapy and allo-HCT offer the potential for cure for most with SCD. However, the cost (∼5 times higher), the current need for myeloablation, and associated late-health effects may make genetic therapies less favorable choices than allo-HCT.