“Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disorder affecting both upper and lower motor neurons. Based on age at onset, site of onset, disease duration, and relative predominance of upper or lower motor neuron signs, clinical manifestations of ALS are very heterogeneous, and different clinical subtypes may be delineated. Although ALS has long been considered a paradigm of pure motor neuron disorder, it has recently been linked to other neurological diseases. Clinical, genetic, and/or neuropathological overlap exists with frontotemporal dementia, distal myopathies, psychiatric disorders, and extrapyramidal syndromes. This clinical heterogeneity can depend on the pleiotropy of ALS-associated genes and by the oligogenic model of disease mechanism. A number of animal models have been created, each of them recapitulating some clinical and neuropathological features of patients. More recently, induced pluripotent stem cells have been used, directly derived from affected patients with different genetic mutations. The combination of animal and cellular models represents an advanced tool that can help to functionally characterize the pathogenetic mechanisms underlying the disease and specifically find efficient and personalized drugs to treat ALS patients”–