Hematopoietic stem cell transplantation is the optimal treatment for patients with primary immunodeficiencies. Best results are achieved with stem cells from a HLA-identical donor, but it is only possible in a small number of patients. Until recently, HLA-mismatched/haploidentical hematopoietic stem cell transplantation was reserved exclusively for patients with severe combined immunodeficiency (SCID). However, as there are many haploidentical donors, it has become the treatment of choice for many other severe primary immunodeficiencies. Apart from appropriate choice of the donor, treatment of infections and pre-transplantation patient conditioning have major impact on transplantation outcome in patients with primary immunodeficiencies.