Acquired Severe Aplastic Anemia (SAA) is an hematological disease characterized by pancytopenia associated with an empty or a fatty bone marrow. Historically the two treatments option have been immunosuppressive therapy (IST) and bone marrow transplantation (HSCT) for patients younger than 40 years, with a HLA identical sibling donor. For patients older than 40 years, IST was the only therapeutic option. In the last two decades, the improved results in the setting of unrelated donor (UD) transplantation have allowed us to introduce UD HSCT in the therapeutic algorithm of SAA. This approach is considered, nowadays, for patients without a sibling donor, aged < 40 years, after failure of a previous course of IST. Likely, in the future, further improvements in the transplant setting, will continue to move up the role of HSCT in the treatment algorithm of SAA.