This article focuses on approaches and techniques for effective cognitive rehabilitation with people who have multiple sclerosis (MS). The patterns of preserved versus disrupted neuropsychological functions are reviewed. The relevant brain anatomy and physiology that underlie the common neurocognitive and neurobehavioral changes are described. The essential role is highlighted of comprehensive neuropsychological, speech language pathology, and clinical evaluations in the design and refinements of cognitive retraining treatment. The functional impact of cognitive problems expected with MS is emphasized, accompanied by examples of cognitive retraining approaches used to manage them and improve day-to-day performance.