Multiple sclerosis is considered an autoimmune disease, which leads to inflammatory demyelinating plaques in the white matter of the central nervous system (CNS). Recent studies on MS pathology, however, show that the disease is complex and heterogeneous. Essentially similar lesions, as those seen in MS, can be induced in experimental animals by auto-immunization with brain antigens. This model, experimental autoimmune encephalomyelitis, thus is commonly used to study pathogenesis of the disease and to test new therapeutic approaches. However, EAE reflects only part of the pathological spectrum of MS. In addition, many different EAE models are available, which cover specific aspects of the disease, but there is no single EAE model, which mimicks MS as a whole. For these reasons EAE, in its broad spectrum, is a useful model to study specific questions of MS pathology and pathogenesis, but its usefulness for testing new MS therapies is limited. In addition, proper selection of the best suited EAE model for a specific study is essential.