Interferon-beta (IFNbeta) is the most widely prescribed disease-modifying therapy for multiple sclerosis (MS) today. Large-scale clinical trials have established the clinical efficacy of IFNbeta in reducing relapses and slowing disease progression in relapsing-remitting MS. IFNbeta therapy was shown to be comparably beneficial for opticospinal MS (OSMS) and conventional MS in Japanese. IFNbeta is effective in reducing relapses in secondary progressive MS and may have a modest effect in slowing disability progression. Clinically isolated syndrome (CIS) refers to an initial demyelinating event that is suggestive of MS. Treatment for CIS with IFNbeta is effective in delaying conversion to clinically definite multiple sclerosis. Since neutralizing antibodies (NAbs) can reduce the clinical efficacy of IFNbeta in patients with MS, clinicians should consider the possible development of NAbs in patients demonstrating disease progression while receiving IFNbeta treatment. In some patients with neuromyelitis optica (NMO)/OSMS patients with anti-aquaporin-4 (APQ4) antibody or longitudinally extensive spinal cord lesions (LESCLs) extending over three vertebral segments as well as in patients with collagen disease, IFNbeta has been found to be ineffective or detrimental. In NMO/OSMS patients with LESCLs or patients with collagen disease, measurement of anti-APQ4 antibody is recommended. In these patients with anti-APQ4 antibody, careful consideration is necessary before initiating IFNbeta treatment.