Amyotrophic lateral sclerosis is a chronic neurodegenerative disorder characterized by selective death of motor neurons and progressive paralysis. Many hypotheses have been proposed to explain its pathogenesis. In recent years, one of the most studied hypotheses was the inflammatory response accompanying the motor neuron death. Microglia and its interactions with motor neurons play important roles in the development and progression of the inflammatory responses and the disease itself, which results in different new and potent therapeutic strategies of great clinical value.