Hematopoietic stem cell (HSC) transplantation is curative therapy for many primary immunodeficiencies. All forms of severe combined immune deficiency (SCID) can be cured, but the extent of the immunologic correction is dependent on the pathophysiology of the primary defect. Defects involving lymphocyte differentiation are more easily corrected than defects in lymphocyte function because a selective advantage exists for the progeny of the normal donor HSC when the primary defect affects lymphocyte differentiation. T-cell-depleted (TCD), haploidentical-HSC transplantation can cure many forms of SCID, but not other primary immunodeficiencies like the Wiskott-Aldrich syndrome (WAS). Unrelated bone marrow and umbilical cord blood are alternative sources of HSC for patients who do not have histocompatible donors.