Multiple sclerosis is a chronic demyelinating disease of the central nervous system. The underlying cause of this disease is not known, but Epstein-Barr virus is thought to be a possible culprit. However, most people infected with this common virus do not develop multiple sclerosis, and it is not feasible to directly demonstrate causation of this disease in humans. Using data from millions of US military recruits monitored over a 20-year period, Bjornevik et al. determined that Epstein-Barr virus infection greatly increased the risk of subsequent multiple sclerosis and that it preceded the development of disease, supporting its potential role in the pathogenesis of multiple sclerosis (see the Perspective by Robinson and Steinman). —YN