Although multiple sclerosis (MS) is a presumed T-cell- mediated disease, it is unclear what triggers the development of neuroantigen-specific T cells. Autoreactive CD4(+) T cells are activated by antigen presenting cells; dendritic cells (DCs) are the primary antigen presenting cells directing T-cell functions and are, therefore, extremely important in directing the immune pathology characteristic of MS. Three important concepts have emerged regarding DCs in MS. First, DCs are present within the healthy central nervous system (CNS) in association with the cerebrospinal fluid space and microvasculature. Therefore, the potential for sampling of CNS antigens in similar fashion to other tissues and organs exists and likely plays an integral role in CNS immunity. The degree of involvement, as well as the source, of these CNS DCs has been addressed by several studies using the experimental autoimmune encephalomyelitis animal model. Second, DCs are found within MS lesions and have been shown to be functionally abnormal in patients with MS. Lastly, therapeutics directed at DCs could potentially be engineered for treatment in MS and in fact may already be involved in the mechanisms of current immunomodulatory therapies.