This chapter discusses multiple sclerosis and other autoimmune and demyelinating disorders. It outlines the etiology, course, prognosis, and differential diagnosis of this group of disorders. It describes the assessment of common deficits that are associated with these groups of neurologic disorders. Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, demyelinating, and degenerative disorder of the central nervous system (CNS) with a heterogeneous clinical presentation. This chapter is an overview of MS for the purpose of informing clinical neuropsychological assessment.