From an epidemiologic perspective, MS is likely a rare complication of Epstein-Barr virus (EBV) infection with risk further modified by vitamin D nutrition, overweight/obesity in childhood or adolesence, and smoking. The latter two risk factros will be discussed in the talk on lifestyle factors and MS risk. This talk will present evidence supporting a causal role for EBV and vitamin D in MS development, and using the Bradford-Hill criteria for assessing causality from epidemiologic studies will argue that these environmental risk facotrs are likely causally related to MS.