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Neuropsychological investigations have demonstrated that cognitive disorders are common (45–65%) in patients with multiple sclerosis. This review summarizes our current understanding of the nature and etiology of these disorders. Specifically, neuropsychological deficits regularly occur on measures of recent memory, attention, information-processing speed, executive functions, and visuospatial perception. In contrast, general intelligence, language, and certain aspects of memory (short-term capacity and implicit) are preserved. The degree and pattern of cognitive dysfunction is highly correlated with the amount and location of white-matter disease within the cerebral hemispheres. Natural history studies indicate that changes in cognitive test performance are correlated with increasing lesion load on magnetic resonance imaging. The development of brief cognitive-testing instruments for clinical screening and measuring treatment effects in clinical trials is underway. A clear weakness in the literature is the dearth of studies evaluating potential treatments for cognitive disorders.