Multiple sclerosis (MS) is a highly debilitating immune mediated disorder of the central nervous system and represents a substantial burden to the developed world. Despite the recent advances in MS research, which risk factors are implicated and how they contribute to MS pathogenesis is largely unknown. However, in line with older studies investigating the genetic and geographical epidemiology of this complex disease, more recent studies have highlighted how MS arises from a combination of genetic susceptibility and environmental exposures acting from gestation to early adulthood. Vitamin D deficiency, season of birth, Epstein Barr virus infection, and smoking behaviour are strongly implicated and able to influence genetic predisposition to MS. Furthermore, these factors appear to act synergistically and the risk of MS in individuals exposed to more than one factor combines multiplicatively. Current evidence suggests that a large part of MS could be prevented and understanding how and when during life risk factors act will ultimately aid the development of prevention strategies.