Amyotrophic lateral sclerosis (ALS) is a worldwide problem with no effective treatment. Patients usually die of respiratory failure. The basic pathological process of ALS is the degeneration and necrosis of motor neurons. Neuroglial cell dysfunction is considered closely related to the development of ALS. Sleep plays an important role in repairing the nervous system, and sleep disorders can worsen ALS. Herein, we review the pathogenesis of ALS and the neuroprotective mechanism of sleep-based therapy. Sleep-based therapy could be a potential strategy to treat ALS.