Interferon-β (IFN-β) is the first therapeutic intervention shown to alter the natural history of multiple sclerosis (MS), a relapsing then progressive inflammatory degenerative disease of the CNS. Since publication of the first randomized placebo-controlled trial of IFN-β, and subsequent acquisition of US and European product licences for use in relapsing–remitting MS, the hopes and expectations of patients have been elevated greatly only to be dampened as more critical analysis of the trial results, in conjunction with the cost of treatment, led to marked limitations on prescription in several countries. IFN-β is not a cure. Here we review what is known about the mechanisms of action of IFN-β in demyelinating disease, and propose a possible model of action of IFN-β in the treatment of MS.