Hematopoietic stem cell transplantation between donors and recipients mismatched on 1 or more HLA alleles has historically been high risk because of complications including GVHD and dysregulated immunity. Studies of donor pools show that if HLA mismatch transplantation were safer, the vast majority of patients could receive a transplant. The Kornblit et al study of nonmyeloablative conditioning with triple-agent immunosuppression in a phase 2 clinical trial shows an improved safety profile that suggests a new option to allow more patients to receive a transplant. MMF, mycofenolate mofetil; TBI, total body irradiation.