Studies in which groups of patients with multiple sclerosis (MS) and controls of comparable age and education are compared reveal consistent impairments by the patient groups on test of anterograde explicit memory, controlled attentional processing, information processing speed, and abstract reasoning and problem solving. Vocabulary, naming and visual perception are less often affected. However, the extent of cognitive impairment for individual patients varies from none at all to global dementia. Both physical and cognitive impairment contribute equally to predicting employment status, but some patients with global cognitive impairment can continue to work effectively at mentally demanding professional jobs. Recently developed screening examinations could detect cognitive impairment early and permit interventions when they should be maximally effective. Three key issues in clinical neuropsychology are identified which have not been addressed by traditional neuropsychology. Italian neuropsychology, because of its unique characteristics, could lead in understanding these important questions.