The therapy of rhinocerebral mucormycosis includes aggressive surgical debridement, administration of high-dose amphotericin B, and control of underlying predisposing conditions, especially diabetes and immunosuppression or immunodeficiency. Hyperbaric oxygen suppresses fungal growth in vitro and has theoretical value in treating mucormycosis because it reduces the tissue hypoxia and acidosis that accompany vascular invasion by the fungus. In a retrospective review of patients at Duke University Medical Center with rhinocerebral mucormycosis, six patients were treated with hyperbaric oxygen and seven cases (involving six patients) were treated without hyperbaric oxygen. All patients received surgical debridement and amphotericin B. Two of six patients receiving hyperbaric oxygen therapy died, and four of seven patients not receiving hyperbaric oxygen therapy died. Adverse effects from hyperbaric oxygen were minimal. Because mucormycosis occurs infrequently, this retrospective review involved a small number of patients. Despite this limitation, adjunctive hyperbaric oxygen appears to be a promising clinical modality for the treatment of rhinocerebral mucormycosis and warrants further investigation.