Motor Neuron Disease (MND) is a fatal neurodegenerative condition, which is 
characterized by the selective loss of the upper and lower motor neurons. At the 
sites of motor neuron injury, accumulation of activated microglia, the primary 
immune cells of the central nervous system, is commonly observed in both human 
post mortem studies and animal models of MND. Microglial activation has been 
found to correlate with many clinical features and importantly, the speed of 
disease progression in humans. Both anti-inflammatory and pro-inflammatory 
microglial responses have been shown to influence disease progression in humans 
and models of MND. As such, microglia could both contribute to and protect 
against inflammatory mechanisms of pathogenesis in MND. While murine models have 
characterized the microglial response to MND, these studies have painted a 
complex and often contradictory picture, indicating a need for further 
characterization in humans. This review examines the potential role microglia 
play in MND in human and animal studies. Both the pro-inflammatory and 
anti-inflammatory responses will be addressed, throughout the course of disease, 
followed by the potential of microglia as a target in the development of 
disease-modifying treatments for MND.