Interferon beta-1b has been shown to reduce the frequency and severity of exacerbations in relapsing-remitting multiple sclerosis (MS). In the North American study, however, approximately 35% of patients developed neutralizing antibodies leading to a diminution of therapeutic efficacy according to current investigations. In contrast, antibody-negative patients showed a 50% reduction in the annual relapse rate compared to patients receiving placebo. Here we provide practical guidelines for neutralizing antibody testing if treatment failure is suspected.