Pseudallescheria boydii is an uncommon cause of central nervous system (CNS) infections. Of a total of 21 cases of CNS infections caused by P. boydii (one described for the first time and 20 reported previously in the English-language literature), eight occurred in immunosuppressed patients and four in patients who nearly drowned; three were trauma related and two were iatrogenic (epidural anesthesia and ventriculoperitoneal shunt, respectively); one occurred in a patient with insulin-dependent diabetes mellitus, and three, in patients without underlying disease or predisposing conditions. The clinical manifestations included brain abscesses (13 cases), spinal pachymeningitis (two cases), chronic meningitis (two cases), intraventricular device-related ventriculitis (two cases), cranial epidural abscess (one case), and acute meningitis (one case). Seven patients showed clinical evidence of extraneural involvement by P. boydii. The outcome is known for 20 patients. Of these, the diagnosis was established while the patient was alive in 18 cases, in spite of which, 15 patients died. All five survivors were managed surgically, and two received intravenous miconazole. P. boydii should be included in the differential diagnosis of CNS infections that occur in the face of immunosuppression, near drowning, and trauma. Occasionally P. boydii can cause CNS infection in the absence of underlying disease or predisposing conditions.