Amyotrophic lateral sclerosis (ALS) has been described by Jean‐Martin Charcot in 1869 and it is now recognized as a multisystem neurodegenerative disorder, with a great heterogeneity involving clinical, genetic, and neuropathological levels. Approximately 10% of all ALS cases have a family history of the disease, while the remaining 90% are sporadic. Most commonly it is diagnosed among people between 40–60 years, but also younger individuals can develop ALS. Two point six individuals/100,000 develop ALS every year and men seem to be more involved than women. The clinical presentation of ALS typically consists of focal muscle wasting (limb muscles) and weakness with progressive spreading. In about 25-30% of cases, ALS patients present a bulbar onset at the beginning. The median survival is about three years. In 10-15 % of cases, ALS coexists with frontotemporal dementia (FTD), a neurodegenerative disorder characterized by behavioral, executive, and/or language impairment. ALS and FTD are now considered two diseases forming a broad neurodegenerative continuum. Currently, there is no cure for moth disorders. The aim of this special issue is to consider the epidemiology of ALS, clinical presentation and manifestation, genetic and sporadic variants and their differences, overlap with FTD disorders, and clinical trials currently recruiting around the world. Case reports, original articles, and reviews of the literature are accepted.