The phenomenon of antibodies to interferon (IFN) beta in patients with multiple sclerosis has attracted the attention of numerous research groups over the years, and has been examined from various different points of view. In this review we describe and discuss some of the aspects that we believe to be most worthy of consideration. The main considerations are as follows: There is a lack of substantial information on the biological/immunological phenomenon of neutralising antibodies in vivo development. Nevertheless, sufficient experimental data are available to provide a rationale for monitoring the presence of anti-IFN antibodies in patients treated with IFN beta; A standardised quantitative assay to detect antibody to IFNs must be agreed. Only when results can be compared, both in terms of the qualitative presence and quantitative measurement of antibodies, will it be possible to monitor fully the ability of antibodies to cause a relapse during treatment; Although there is increasing evidence to indicate that the development of antibodies to IFN beta may be associated with a failure of the beneficial effects of the therapy, the use of the seropositivity for neutralising antibodies to IFN beta as the only surrogate marker for clinical and therapeutic decision-making is questionable.