Interferon beta was the first therapy to be approved for the treatment of relapsing-remitting multiple sclerosis (MS) more than 10 years ago. Interferon beta reduces relapse rates and disease burden and activity, and it may have beneficial effects on the progression of long-term disease disability. The occurrence of neutralising interferon-beta antibodies has been postulated as a possible cause of the failure of interferon beta in some patients with MS. Here we discuss the basic mechanisms that may account for the generation of an interferon-beta antibody response and its biological implications. We review the evidence for neutralising antibodies as a consequence of interferon-beta treatment, and discuss the implications for the treatment of MS. Strategies to assess and manage the long-term impact of neutralising antibodies will be outlined.