Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and microglia and macrophages play important roles in its pathogenesis. The activation of microglia and macrophages accompanies disease development, whereas depletion of these cells significantly decreases disease severity. Microglia and macrophages usually have diverse and plastic phenotypes. Both pro-inflammatory and antiinflammatory microglia and macrophages exist in MS and its animal model, experimental autoimmune encephalomyelitis. The polarization of microglia and macrophages may underlie the differing functional properties that have been reported. in this review, we discuss the responses and polarization of microglia and macrophages in MS, and their effects on its pathogenesis and repair. Harnessing their beneficial effects by modulating their polarization states holds great promise for the treatment of inflammatory demyelinating diseases. Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and microglia and macrophages play important roles in its pathogenesis. The activation of microglia and macrophages accompanies disease development, while depletion of these cells significantly decreased disease severity. Microglia and macrophages both have-diverse and plastic phenotypes. Both pro-inflammatory and antiinflammatory microglia and macrophages exist in MS and its animal model, experimental autoimmune encephalomyelitis. The polarization of microglia and macrophages may underlie the differing functional properties that have been reported. in this review, we discuss the responses and polarization of microglia and macrophages in MS, and their effects on its pathogenesis and repair. Harnessing their beneficial effects by modulating their polarization states holds great promise for the treatment of inflammatory demyelinating diseases.