Acquired severe aplastic anemia can be treated successfully with either immunosuppressive therapy or bone marrow transplantation. Although immunosuppressive therapy can be readily administered to all patients, it is not a curative approach and is associated with a higher risk of clonal evolution than is transplantation, which yields rapid and long-lasting hematologic remission. This article reviews the key diagnostic and prognostic factors that influence the choice of therapy in patients with acquired aplastic anemia.