Amyotrophic lateral sclerosis (ALS) is a progressive, degenerative disease of the motor system characterized by signs and symptoms of upper and lower motor dysfunction. This results in the presence of focal amyotrophies and pareses affecting voluntary muscles. Patients die after a few years, in most cases by respiratory failure. ALS is the most frequent motor neuron disease; however, its etiology and pathogenesis are only known in fragments. Its genetic basis is only partially understood and major gaps remain in the understanding of its pathogenesis with the basic principle of selective vulnerability and potentially resulting therapeutic consequences.