Multiple sclerosis (MS) is a common, complex neurological disease. Epidemiological data implicate both genetic and environmental factors in the etiology of MS, with various factors interacting with one another. Environmental exposures might occur long before the disease becomes clinically evident, as suggested by the wide range in onset age. In this Review, we examine the key time periods during which the environment might contribute to MS susceptibility, as well as the potential environmental factors involved. Understanding the nature of environmental influences in MS is highly relevant to the development of public health measures that are aimed at preventing this debilitating disease.