Although the role of Epstein-Barr virus (EBV) in autoimmunity is biologically plausible and evidence of altered immune responses to EBV is abundant in several autoimmune diseases, inference on causality requires the determination that disease risk is higher in individuals infected with EBV than in those uninfected and that in the latter it increases following EBV infection. This determination has so far been obtained compellingly for multiple sclerosis (MS) and, to some extent, for systemic lupus erythematosus (SLE). In contrast, evidence is either lacking or not supportive for other autoimmune conditions. In this chapter, we present the main epidemiological findings that justify these conclusions and their implications for prevention and treatment.