Refractory aplastic anemia (AA) is defined as lack of response to first line immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and ciclosporin (CSA) and manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the last two decades with overall 5-year survival reaching 57% during 2002-2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional marrow failure masquerading as apparent idiopathic AA should be done in conjunction with centres of excellence. Hematopoietic stem cell transplant (HSCT) is indicated if refractory AA patients are fit for HSCT and have a suitably matched donor, either sibling (>40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of ATG + CSA, although response in the refractory setting is only around 30-35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic, eltrombopag, in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.