We report the outcome of a 43 year old man who developed fatal ventriculoencephalitis due to cytomegalovirus (CMV) infection 7 months post allogeneic stem cell transplant. He failed multiple lines of treatment, including intravenous ganciclovir, foscarnet, and CMV-specific immunoglobulins, without improvement in CSF CMV copies. Novel intrathecal administration of CMV immunoglobulins was given but did not lead to clearance of CMV from CSF. No adverse effects related to intrathecal CMV immunoglobulins were observed. Notably, throughout this period, CMV in blood remained undetectable. This case highlights the difficulty in treating CMV encephalitis, and that novel therapeutic approaches are needed.