A previously healthy 47-year-old man with coccidioidal meningitis had fluconazole treatment failure and developed severe symptoms, multiple cranial nerve palsies, and brain-stem inflammation visible on magnetic resonance imaging (MRI). High-dose voriconazole therapy resulted in gradual resolution of almost all signs and symptoms, normalization of cerebrospinal fluid, and clearing of brain-stem edema seen on MRI. The patient had photosensitivity after 10 weeks of treatment, but this improved when the voriconazole dose was lowered. Continuous voriconazole therapy kept coccidioidal meningitis in complete remission in this patient for >2 years.