Rhinocerebral mucormycosis (RCM) is an invasive fungal infection that necessitates, in most cases, aggressive surgical debridement and high cumulative, often nephrotoxic doses of amphotericin B. A 50-year-old woman with RCM was treated successfully with amphotericin B lipid complex as primary therapy. The patient previously had displayed progressive intracranial involvement and rising serum creatinine levels while receiving the conventional (nonlipid) form of amphotericin B. A literature review identified only a few cases where systemic antifungal therapy was administered, with minimal or no surgery. Our case further supports that amphotericin B lipid complex can be used as primary therapy in selected patients with RCM, without the need for surgical exenteration.