Advances in hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have improved survival in severe aplastic anemia (SAA) from 10%-20% in the 1960s to 80%-90% today. A matched sibling HSCT is the treatment of choice in younger patients, whereas IST is often used in older patients or in those who lack a histocompatible sibling. Graft rejection, GVHD, and poor immune reconstitution (with associated infectious complications) limit the success of HSCT, whereas lack of response, relapse, and clonal evolution limit the success of IST. The historically high rate of graft rejection in SAA is now less problematic in the matched setting, but with greater rates observed with unrelated and umbilical cord donors. The correlation of increasing age with the risk of GVHD and the significant morbidity and mortality of this transplantation complication continue to affect the decision to pursue HSCT versus IST as initial therapy in adults with SAA. Outcomes with matched unrelated donor HSCT have improved, likely due to better donor selection, supportive care, and improved transplantation protocols. Results with mismatched unrelated donor and umbilical HSCT are not as favorable, with higher rates of graft rejection, GVHD, and infectious complications. Investigation of several upfront alternative IST protocols has not improved outcomes beyond horse antithymocyte globulin and cyclosporine. More recently, the role of alemtuzumab in SAA has been better defined and an oral thrombomimetic, eltrombopag, is showing promising activity in refractory cases. The most recent advances in HSCT and IST in SAA are discussed in this review.