The exact role of environmental risk factors in the etiology of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) is still unknown. Their hypothetical contribution ranges from a minimal impact to a major role. Among the environmental factors strictu sensu (i.e., not life-style factors) suspected to play a role in ALS etiology, we consider pesticides, the metalloid selenium, some heavy metals, magnetic fields and cyanobacteria. However, the possibility exists that these factors exert their activity only in genetically susceptible persons and only after long-term exposures, thus further hampering epidemiologic studies. The recent availability of powerful tools such as population-based ALS registries for case ascertainment and clustering detection, and of environmental modeling techniques and of geographical information systems, may yield unique opportunities for offering insight into the etiology of the disease.