Personality assessment is a potentially important component of clinical and empirical work with neurological patients because (a) individual differences in personality may be associated with different neurological outcomes and (b) central nervous system changes may give rise to alteration in personality. For personality assessment to be useful to clinicians and researchers, the tests must be reliable and valid, as self-report measures require certain baseline levels of comprehension and insight, both of which can be compromised by cerebral disease. In this study, the authors examined the psychometric properties of the widely used NEO Five-Factor Inventory in a group of 419 patients with multiple sclerosis. Their objective was to determine if the NEO Five-Factor Inventory is reliable and valid in this population. Results showed adequate estimates of internal consistency, factorial validity, and self-informant correlation that support its use with patients with multiple sclerosis. Implications, limitations of the current study, and directions for future research are discussed.