Multiple sclerosis (MS) is the most frequent, demyelinating disease of the central nervous system (CNS) in Northern Europeans and North Americans. Despite intensive research its etiology is still unknown, but a T cell-mediated autoimmune pathogenesis is likely to be responsible for the demyelination. This hypothesis is based both on findings in MS patients and studies of an experimental animal model for demyelinating diseases, experimental allergic encephalomyelitis (EAE). Experiments in EAE have not only demonstrated which myelin antigens are able to induce the demyelinating process but also have determined the characteristics of encephalitogenic T cells, that is, their fine specificity, major histocompatibility complex (MHC) restriction, lymphokine secretion, activation requirements, and T cell receptor (TCR) usage. Based on these findings, highly specific and efficient immune interventions have been designed in EAE and have raised hopes that similar approaches could modulate the disease process in MS. Although the examination of the myelin-specific T cell response in MS patients has shown parallels to EAE, this remains an area of intensive research because a number of questions remain. This review summarizes the important lessons from EAE, examines recent findings in MS, and discusses current concepts about how the disease process develops and which steps might be taken to modulate it.