Observational studies document a positive relationship between vitamin D from the environment (sunlight or diet), circulating vitamin D status, and improved symptoms or prevention of multiple sclerosis (MS). Experimental animal models of MS reproduce the beneficial effects of vitamin D and 1,25(OH)(2)D(3). The geographical distribution of MS can be explained by both the hygiene hypothesis and the vitamin D hypothesis. It therefore seems more likely that both hypotheses may be correct and that there are interactions between multiple environmental factors like vitamin D and the rate of infection that might explain the etiology of MS. The effects of vitamin D on the immune system and in the CNS have begun to be described and there is some information on the mechanisms underlying the effects of vitamin D in MS. A need exists for better understanding of the interactions of the environmental factors on MS, communication with the physicians treating MS patients as to the benefits of vitamin D, and clinical interventions with both vitamin D and analogs of 1,25(OH)(2)D(3).