As the most common non-traumatic disabling disease among adolescents, multiple sclerosis (MS) is a devastating neurological inflammatory disease of the central nervous system. Research has not yet fully elucidated its pathogenesis, but it has shown MS to be a complex, multifactorial disease with many interplaying factors. One of these factors, natural killer (NK) cells, lymphocytes of the innate immune system, have recently gained attention due to the effects of daclizumab therapy, causing an expansion of the immunoregulatory subset of NK cells. Since then, NK cells and their relation to MS have been the focus of research, with many new findings being published in the last decade. In this review, NK cells are pictured as potent cytotoxic killers, as well as unique immune-regulators. Additionally, an overview of our current knowledge regarding NK cells in MS is given. The role of NK cells in MS is reviewed in the context of well-established environmental factors and current disease modifying therapies to gain further understanding of the pathogenesis and treatment options in MS.