microRNAs play a fundamental role in the immune system. One particular microRNA, miR-155 plays a critical role in hematopoietic cell development and tightly regulates innate and adaptive immune responses in response to infection. However, its dysregulation, more specifically its overexpression, is closely associated with various inflammatory disorders. The purpose of this review is to consolidate how miR-155 underpins a variety of processes that contribute to the pathology of multiple sclerosis (MS). In particular, the impact of miR-155 is discussed with respect to human pathology and animal models. How miR-155 contributes to the activation of pathogenic immune cells, the permeability of the blood-brain barrier, and neurodegeneration in relation to MS is described. Many environmental risk factors associated with MS susceptibility can cause upregulation of miR-155, while many of the current disease-modifying treatments may work by inhibiting miR-155. From this review, it is clear that miR-155 is a realistic and feasible diagnostic, prognostic, and therapeutic target for the treatment of MS.