Multiple sclerosis (MS) is a debilitating CNS disease characterized by demyelination and neuro-axonal loss. Though the exact etiology is still unknown, accumulated evidence points to the immune system being involved in the MS disease-process. Both ill-fated adaptive and innate immune responses can potentially contribute to the etiopathogenesis. We have been interested in deciphering how innate immunity might be involved; in particular, the role of γδ T cells. In this review, we discuss the current understanding about γδ T cells and describe the evidence implicating them in myelin injury, neurotoxicity, and immunoregulation in the development of MS.