Purpose: To present a case report and literature review of Scedosporium apiospermum endophthalmitis and related infections. Methods: A case report was evaluated. Results: A 59-year-old Trinidadian woman with chronic endophthalmitis following cataract surgery presented for evaluation in the United States. Prior to presentation, she had been treated with intravitreal (IVT) vancomycin and had undergone 2 pars plana vitrectomies (PPVs). Examination revealed hand motion vision, significant anterior chamber inflammation with a hypopyon, and posterior chamber inflammation without retained lens fragments. After failing treatment with topical steroids and IVT antibiotics, she underwent repeat PPV, vitreous biopsy, anterior chamber washout, and intraocular lens removal with the capsular bag. Intraocular cultures were positive for Scedosporium apiospermum sensitive to voriconazole. The patient was successfully treated with oral voriconazole. Conclusions: Fungal endophthalmitis should be considered in patients with chronic endophthalmitis refractory to IVT antibiotics.