Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system with a complex immune nature and varied clinical presentation. Current therapies for MS are limited by toxicity and efficacy, so interest has now turned to specifically modulating autoreactive T-cell responses. Murine MS models, such as experimental autoimmune encephalomyelitis (EAE), have proved invaluable for understanding the immune components of MS and for designing and testing potential immunotherapies. Here, we review the current knowledge of the mechanisms of induction and progression of EAE and MS and the immunotherapies that have resulted from studies of the EAE model.