Treatment of multiple sclerosis (MS) with interferon beta (IFNbeta) can be associated with the development of binding antibodies (BAbs) and neutralizing antibodies (NAbs). NAbs are a subset of BAbs that prevent IFNbeta from effectively binding to or activating its receptor, thereby blocking its biologic effects and inhibiting its therapeutic effects. Several factors can affect the incidence and titers of NAbs that develop to IFNbeta, including the type of IFNbeta preparation used for treatment. One of the major limitations to evaluating the relative importance of these factors is the variation in assays used to detect IFNbeta antibodies. Two major types of assays are used to detect antibodies to IFNbetas: [1] binding assays, which measure the ability of antibodies in patients' sera to bind to IFNbeta; and [2] neutralization assays (or bioassays), which measure the ability of patients' sera to neutralize the biologic effects of IFNbeta. Assays used to detect NAbs differ in their sensitivity and specificity, and there can be high variability between laboratories in how these assays are performed (e. g., types of cells, quantity of IFNbeta). This article reviews assays currently used for detecting NAbs to IFNbeta and discusses the development of an international standard NAb assay. The myxovirus resistance protein A (MxA) assay is recommended as the standard assay for the quantification of NAbs providing availability of reagents.