OBJECTIVE: Invasive sino-orbital fungal infections are life-threatening complications of immunonosupression that are difficult to treat. Currently there are no standard treatment guidelines. The most widely accepted therapy includes parenteral anti-fungal therapy and surgical debridement of sinuses with orbital exenteration, a procedure that is not only disfiguring, but may increase morbidity. Injection of retrobulbar Liposomal Amphotericin B (L-AMB) is an alternative approach that provides local administration to infected tissues. The adjunct use of anti-fungal retrobulbar injections not been extensively reviewed in treating sino-orbital infection. We are reporting the multimodal approach of using L-AMB retrobulbar injections in combination with sinus debridement, intravenous (IV) anti-fungal therapy, and hyperbaric oxygen (HBO) for the management of sino-orbital infection. METHOD & RESULTS: Review of literature of 12 cases and retrospective evaluation of one patient with sino-orbital Aspergillus flavus infection on chemotherapy for T-cell acute lymphocytic leukemia treated with retrobulbar Amphotericin B, IV anti-fungal agents, and hyperbaric oxygen therapy. Clinical characteristics, radiographic features, management techniques, and clinical outcomes are described. CONCLUSION: Retrobulbar Amphotericin B injection may be an effective adjunct to hyperbaric oxygen and parenteral anti-fungals in the control of sino-orbital fungal infections.