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Multiple sclerosis is the most common cause of non-traumatic neurological disability affecting young adults in the northern hemisphere. Recent technological advances in immunology, molecular biology and neuroimaging have accelerated our understanding of the pathogenesis of this disorder. Improvements in clinical trial methodology will soon allow researchers to test therapeutic agents in a fraction of the time traditionally required to study therapeutic claims in multiple sclerosis. The recent approval of interferon beta-1b by the US Food and Drug Administration has already had a profound effect on clinical trials in progress and on the manner in which neurologists in the US treat multiple sclerosis outside the confines of clinical trials. It will certainly be difficult to perform placebo-controlled clinical trials in the future.In light of these recent advances, we review the clinical experience of immunosuppressive and immunomodulatory therapies that have progressed beyond the pilot stage of testing. These therapies include azathioprine, copolymer I, corticosteroids, cyclophosphamide, cyclosporin, interferon-β, plasma exchange and total lymphoid irradiation. For each therapy a discussion of the potential mechanism of action is followed by a critical review of the pertinent clinical experience. Each section concludes with a commentary regarding the potential or proven risks and benefits of each therapy.