Pure red cell aplasia (PRCA) is a type of bone marrow failure syndrome (stem cell failure) and is characterized by severe normocytic, normochromic anemia associated with reticulocytopenia and the absence of erythroblasts in otherwise normal bone marrow. The acquired form of chronic PRCA may present as a primary hematological disease in the absence of any other diseases or secondary to thymoma, lymphoproliferative disorders, infections and collagen vascular diseases or after exposure to various drugs or chemicals. Thus, identifying the cause of PRCA is crucial for the optimal management of this disorder. Idiopathic PRCA and secondary PRCA refractory to treatment of the underlying diseases are both generally treated as an immune-mediated disorder. Most chronic PRCA patients successfully treated with immunosuppressants require maintenance immunosuppressive therapy. Refractoriness to induction immunosuppressive therapy and relapse of anemia may be risk factors for death in idiopathic, thymoma-associated and large granular lymphocyte leukemia-associated PRCA. The major causes of death are infections and organ failure. Standard treatment options for refractory and relapsed PRCA patients and the immunopathophysiology of acquired chronic PRCA merit further research.