<i>Background and Methods:</i> To evaluate the value of brain biopsy for neurology patients in our unit, we conducted a retrospective audit of neurology patients referred for brain biopsies for non-neoplastic disease from 1993 to 2007. <i>Results:</i> 64 patients [median (range) age 51 (16–74) years] were included. The clinical presentation was diffuse encephalopathy for 40 patients, focal for 13 and multifocal for 11. The biopsy was diagnostic in 34 patients, abnormal but non-diagnostic in 21 and normal in 9. There was a statistically significant association between clinical presentation and biopsy result (p = 0.004); diagnostic biopsies were more common in patients with focal or multifocal clinical presentations. Twenty patients (31%) had alterations of management as a result of their brain biopsy, comprising specific treatment (11 patients) or prognosis/diagnosis of untreatable conditions (9 patients). Diagnoses of treatable conditions included Whipple’s disease, tuberculoma, progressive multifocal leukoencephalopathy, and neurosarcoidosis. Five patients (7.8%) had complications. <i>Conclusions:</i> Brain biopsy is useful and relatively safe in the management of neurology patients, with a diagnostic yield of 53% in our series; some led to significant changes in management, including treatment of infections. Patients with focal or multifocal presentation are more likely to yield a diagnostic biopsy result.