Substantial phenotypic heterogeneity exists in individuals who are homozygous for the sickle gene mutation. GWAS of patients with severe sickle cell disease have the potential to identify single-nucleotide polymorphisms that are associated with disease severity. Recent work has identified the importance of bcl11A in fetal hemoglobin silencing. In sickle cell disease transgenic mice, inactivation of bcl11A corrected the hematologic defects of sickle cell disease by increasing Hb F production. Both of these are exciting advances in the science of sickle cell disease that would be of interest to the AABB audience.