Multiple sclerosis (MS) is an inflammatory central nervous system (CNS) demyelinating disease, though the etiology still remains unknown. To make a diagnosis of MS is largely based on clinical features which are characterized by multiplicity of CNS symptoms and signs in time and space. However, there have been some questions and problems about the diagnosis of MS. There are a great diversity of MS clinical forms, such as relapsing and remittent type, chronic progressive type (primary or secondary), Devic type or Balo type, so on. In particular, optic-spinal form of MS is undoubtedly common in Japan and other Asian countries, compared with American and Northern European countries. To make a correct diagnosis of MS, it is important to rule out other diseases mimicking MS, such as tumors, cerebrovascular diseases, several myelopathies, collagen diseases, sarcoidosis, Wilson disease, so on. Nevertheless, it is hard to differentiate MS from some other MS-mimicking diseases, for example CNS Sjögren disease and antiphospholipid antibody syndrome. Since MRI detects demyelinating lesions within CNS with high sensitivity, MRI examination has a great impact on the diagnosis, etiological investigation and therapeutic trial of MS.