Our objective was to examine trends and epidemiology of amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) associated deaths in the United States. ALS/MND associated death rates and trends in the United States for 1999-2009 were examined using the multiple cause-of-death mortality data. Age-specific and age-adjusted death rates were calculated. For 1999-2009, the average annual age-adjusted death rate was 2.17/100,000 persons. The age-specific rate increased with age until 75-79 years. Males experienced a higher death rate than females. There was no definitive trend in the annual ALS/MND associated death rate, although analyses suggested a possible decrease (p = 0.05); however, the rate increased for persons 20-49 years of age and declined for persons ≥ 65 years of age. The annual rate for males decreased whereas the rate for females showed no change. In conclusion, the suggested decreasing annual ALS/MND associated death rate for 1999-2009 contrasts with earlier reports indicating that the incidence and death rate of ALS were increasing. While the ALS/MND associated death rate slightly increased among adults 20-49 years of age, rates declined among two subpopulations at higher risk for ALS/MND--males and persons ≥ 65 years of age. Continued monitoring of ALS/MND mortality data and additional epidemiological studies will be important to further elucidate these epidemiological trends.