This chapter provides an introduction to the history of MS. It explores the observations of multiple sclerosis that were made even before the disease was more formally framed and named by Charcot in 1868. It reviews how description of the disease advanced through the 20th century, and how classification of clinical disease types, development of various tests, and the advent of magnetic resonance imaging improved diagnosis. Early attempts at therapy are discussed and contrasted with the modern disease modifying agents that were introduced in 1993.