The development of neutralising antibodies (NABs), or neutralising activity in the absence of NABs, is a potential complication of therapy with interferon (IFN)-beta for patients with multiple sclerosis, limiting therapeutic efficacy. Discontinuation of IFN-beta therapy in patients found to have sustained titres of NABs > 1:100 over an interval of 3 - 6 months has been recently proposed as a Level A recommendation. The extent to which NABs are causative, rather than an epiphenomenon, in determining drug failure has been a matter of numerous investigations and is still controversial. Thus, further studies are warranted for determining the role that NABs may play in reducing the response to the drug. In particular, the effects of NABs in reducing the efficacy of IFN-beta therapy beyond clinical relapse rate and lesion load on conventional imaging are not as yet fully understood.