Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a degenerative disease of motoneurons. The reduced number of motoneurons in the brain and spinal cord causes a progressive reduction in the innervation of muscles, resulting in immobility and finally complete paralysis of respiratory muscles. The life expectancy of ALS patients after diagnosis is low and ranges between an estimated three to five years. The exact cause for the loss of motoneurons is unknown. Factors are discussed as triggers for the onset of ALS, including oxidative stress, loss of neurotrophic factors, glutamate neurotoxicity, and neuroinflammation. About ten percent of ALS cases show a familial background. In some of these patients, a dominant mutation of the Cu/Zn superoxide dismutase (SOD-1) gene has been identified. The understanding of ALS as a genetic disease has mainly contributed to the knowledge about molecular processes in ALS, allowing the development of targeted pharmacological therapies for the protection of motoneurons. The only approved therapy to date (riluzole) reduces the toxic effects of glutamate release. Although riluzole prolongs the survival in some patients for several weeks, it is associated with severe side effects and has no effect on already existing symptoms.