Severe aplastic anemia (SAA) is a BM failure syndrome in which allo-SCT remains a highly effective curative option. Its application remains limited by donor availability and by the potential for treatment-related morbidity and mortality. The improved outcomes with unrelated transplantation are a result of the advent of molecular donor-recipient matching, generation of effective novel conditioning regimens, improvement of supportive care and expansion of the donor registry. Decision making regarding the earlier use of unrelated transplant procedures is rapidly evolving. This paper reviews critical data relevant to these treatment options and recommends early consideration of related SCT for patients with SAA who show failure of immune suppressive therapy.