Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS) in the Western world. The disease is characterized histologically by the infiltration of encephalitogenic 1/ 17-polarized CD4⁺ T cells, B cells, and a plethora of myeloid cells, resulting in severe demyelination ultimately leading to a degeneration of neuronal structures. These pathological processes are substantially modulated by microglia, the resident immune competent cells of the CNS. In this overview, we summarize the current knowledge regarding the highly diverse and complex function of microglia during CNS autoimmunity in either promoting tissue injury or tissue repair. Hence, understanding microglia involvement in MS offers new exciting paths for therapeutic intervention.