Cognitive function is often impaired in multiple sclerosis (MS) patients. Cognitive dysfunction occurs in half of all MS patients. Cognitive impairment is the direct result of MS related cerebral pathology. Cognitive dysfunction is typically evaluated by a board-certified clinical neuropsychologist. The purposes of such an evaluation can be varied and involve questions of differential, disability assessment, design of cognitive rehabilitation interventions, and clinical management with symptomatic and disease-modifying drugs. Patients enrolling in these symptomatic trials were required to have documented cognitive deficits or at minimum subjective cognitive complaints. The typical trial involved a relatively small number of patients and was conducted at a single site, although larger, multisite trials have begun to appear in the literature. Results of these trials have been mixed. Medications approved for the treatment of Alzheimer’s disease (donepezil, rivastigmine, memantine) show either no clinical benefit or a very modest benefit in treating MS related cognitive dysfunction.