This case study shows that rituximab-resistant AIHA in young children represents a significant challenge, requiring aggressive immunosuppressive therapy, which may potentially cause severe life-threatening complications. Nowadays, it is not clear which is the best immunosuppressive agent to be administered in the event of rituximab failure. We found that the combination of methylprednisolone and cyclophosphamide could be a valid alternative, based on previous experience. Nevertheless, a universal therapeutic flow-chart is still lacking and should be defined, which considers new therapeutic strategies such as alemtuzumab [11] or hematopoietic stem cell transplantation [12] . What is clear, however, in the case of heavy immunosuppressive therapy, is the importance of strict patient monitoring during and after immunosuppressive therapy and an antimicrobial prophylaxis, particularly for fungal agents and P. jirovecii.