Secreted and cell surface molecules that control the nature of immune responses or directly mediate tissue damage are important targets for therapeutic intervention of autoimmune inflammatory disorders. The precise aetiology of multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system is unknown and therapeutic interventions for this disease are limited. However, as it is believed that MS is autoimmune in nature, it seems likely that targeting of the immune system, either to deviate it down a more benign pathway or to directly block tissue damaging effector mechanisms, may enable this disease to be controlled. In this overview we examine three alternative approaches to therapy of MS: cytokine-directed immune deviation, immunoregulation by type I interferons and blockade of TNF. Underlying rationales for the application of these approaches to the treatment of MS are based largely on studies in the disease model experimental autoimmune encephalomyelitis. These studies are reviewed.