Abstract: Amyotrophic lateral sclerosis (ALS) is classified as a multigenic, multifactorial, and heterogeneous neurodegenerative/neuroinflammatory disease that slays especially upper and lower motor neurons controlling voluntary muscle activity. After the insurgence that is characterized by typical symptoms such as weakness in the limbs and muscle twitches, the disease rapidly evolves into progressive muscle atrophy, paralysis, and lastly death occurring by respiratory failure usually within 2–4 years of diagnosis. ALS is now understood as a multisystem and broad-spectrum motor neuron disease largely variable in presentation and outcomes, also showing extra-motor deficits such as extrapyramidal, thalamic, cerebellar, and sensory nerve abnormalities, in addition to comorbid cognitive-behavioral instabilities and psychiatric symptoms. Approximately 15% of ALS patients are also reported suffering from frontotemporal dementia. Concomitant immunological irregularities and gut dysbiosis are often observed. The autonomic nervous system is also involved in the disease, since patients die of sudden death when they lose their ability to compensate for cardiorespiratory arrest. It clearly emerges that a disease like ALS impacts multiple systems throughout the body, and it is not just a neurological disorder.