Chronic invasive Aspergillus sinusitis is a rare and potentially devastating infection. Management typically requires extensive surgical debridement followed by long-term antifungal therapy, primarily with intravenous amphotericin B. We describe the case of an elderly woman who had been diagnosed with extensive Aspergillus sinusitis that had invaded critical structures. The extensiveness of the infection and the patient's frailty and unwillingness to undergo a disfiguring procedure precluded surgery, and her medical condition was too fragile to withstand amphotericin B therapy. Therefore, we decided to treat her with a combination of caspofungin and voriconazole, two relatively nontoxic antifungal agents that have different mechanisms of action. After administration of this novel regimen, the infection resolved rapidly.