Encephalopathy following Ifosfamide treatment is a well-described phenomenon that is commonly treated with Methylene Blue (MB). The course of encephalopathy and MB therapy has not been described in the literature as lasting longer than 30 days following treatment cessation. We present the case of an 11-year-old female with recurrent episodes of severe somnolence for five months following Ifosfamide-containing chemotherapy for her germ cell tumor. Administration of MB gave immediate but limited response. Our novel case continued to require treatment for 5 months following cessation of therapy. We hypothesize that a genetic component confers increased susceptibility to Ifosfamide-induced encephalopathy.