A 17-year-old girl developed invasive rhinocerebral mucormycosis during intensive re-induction chemotherapy for relapsed pre-B acute lymphoblastic leukemia. Due to the high case fatality rate for invasive mucormycosis in profoundly immunosuppressed patients, an aggressive treatment regimen was pursued. In addition to the standard of care treatments with intravenous amphotericin and aggressive surgical debridements, she received intraventricular amphotericin to the brain via an Ommaya reservoir, hyperbaric oxygen treatments, filgrastim, intravenous immunoglobulin and antifungal in vitro synergy testing to allow for more targeted antifungal therapy with the addition of micafungin. After a 3-month treatment course, it was determined that her mucormycosis was under appropriate control, allowing her to continue treatment for her leukemia with hematopoietic stem cell transplant with a plan for continued intravenous antifungal therapy through engraftment.