The etiology of sporadic amyotrophic lateral sclerosis (ALS), the most common form of this degenerative disease of the motor neurons, is still unknown, despite extensive investigation of several genetic and environmental potential risk factors. We have reviewed laboratory and epidemiological studies assessing the role of exposure to neurotoxic chemicals (metalloid selenium; heavy metals mercury, cadmium, and lead; pesticides) in ALS etiology by summarizing the results of these investigations and examining their strengths and limitations. Despite limitations in the exposure assessment methodologies typically used in human studies, we found suggestive epidemiological evidence and biologic plausibility for an association between ALS and antecedent overexposure to environmental selenium and pesticides. The relation with mercury, cadmium, and lead appears weaker.