Hematopoietic cell transplant recipients with existing "difficult" antibodies such as multiple alloantibodies or an antibody directed to a high prevalence antigen can result in complex challenges regarding the provision and transfusion of rare red cells, particularly if the patient requires very rare blood and/or if the patient requires long-term support. Most frequently the donor cells are incompatible with the patient's antibody as well. Dilemmas regarding how long or if to honor the pre-existing antibodies, how hard to look for sub-clinical detectable antibodies and what happens when antibodies are formed by the transplanted cells to host red cell antigens often present in these cases. Because the red cells may be difficult to locate for repeated transfusion, the presentation will include a brief summary of the American Rare Donor Program, a program which manages rare blood needs in the USA. The role of the WHO International Rare Donor Panel and the ISBT Working Party will also be discussed.