Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder of unknown etiology. ALS onset is rare before age 40 and increases with age thereafter. Men are at higher risk than women (ratio 1.3:1). Other than age and gender, the only indisputable risk factor for ALS is genetic susceptibility, with familial cases occurring in about 10% of most case series. Genetic linkage studies have provided evidence that a mutant form of the gene that codes for Cu/Zn superoxide dismutase, an endogenous free radical scavenger, is important in 15-20% of familial cases. Epidemiologic studies have identified associations of sporadic ALS with work in occupations that involve toxicant exposure. Environmental toxicants may act against a background of increased genetic susceptibility; however, genetically acquired biochemical defects have not been identified in sporadic ALS patients. Other epidemiologic theories of disease etiology have emphasized the potential role of physical trauma, electrical shock, and vigorous physical exertion, but evidence regarding these factors is inconsistent.