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Secondary progressive multiple sclerosis (SPMS) is a form of MS characterized by continuously worsening disability with or without superimposed relapses that occurs after a variable period of relapsing remitting disease and results in limited ambulation for almost all patients. The use of interferon beta (IFN β) for immunomodulation in patients with SPMS has been evaluated in four recent clinical trials: The European multicentre trial on IFN β-1b in SPMS (EUSPMS), the Secondary Progressive Efficacy Trial of Rebif (IFN β-1a) in MS (SPEC TRIMS), the North A merican Study of IFN β-1b in SPMS (NA SPMS), and the Internatio nal MS Secondary Progressive Avonex C linical Trial (IMPACT). EUSPMS was the only trial to demonstrate a significant positive effect of therapy on disease progression as measured by the expanded disability status scale (EDSS). However, results from all studies demonstrated significant positive effects of treatment on relapse, T2 lesion load, and gadolinium enhancement. Immunomodulation with IFN β has the potential to significantly slow disease progression and improve quality of life for patients with SPMS. While results with monthly IV Ig were disappointing, positive effects on disease progression have been reported with the applicatio n of immunosuppressants, especially Mitoxantrone. The risk-benefit ratio of these cytostatic agents remains controversial. New strategies addressing the important neurodegenerative aspects of the disease are urgently needed. [ABSTRACT FROM AUTHOR]