Because Pseudallescheria boydii vertebral osteomyelitis is rare and frequently resistant to available antifungal agents, the proper treatment of this lesion has not been defined. To better determine the best treatment of this lesion, the authors evaluated a case P. boydii vertebral osteomyelitis and reviewed the literature. A 48-year-old man had isolated thoracic vertebral osteomyelitis resulting from P. boydii and associated severe thoracic back pain and proximal lower extremity pain and weakness. Magnetic resonance imaging studies revealed continued collapse of the T6--T7 vertebrae despite previous posterior debridement and appropriate antifungal chemotherapy. On admission to the authors' institution, the patient underwent a right thoracotomy, anterior debridement with transthoracic T6--T7 corpectomies and strut grafting, followed by posterior fusion and stabilization with pedicle screws. After operation, the patient's pain, hyperalgesia, and lower extremity symptoms resolved. He was treated with a 12-month course of itraconazole. Imaging and laboratory studies show no evidence of recurrence. P. boydii vertebral osteomyelitis can have devastating neurologic sequelae if not treated properly. The frequent lack of response of this unusual fungal infection to systemic therapy requires frequent serial follow-up examinations. Patients with evidence of progression on imaging studies or neurologic findings should undergo early and aggressive surgical debridement.