Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged ≥60 years, and those with a family history of ALS are more likely to develop the disease (2). No cure for ALS has yet been identified, and the lack of proven and effective therapeutic interventions is an ongoing challenge. Treatments currently available, Edaravone and Riluzole, do not cure ALS, but slow disease progression in certain patients (3,4). This report presents National ALS Registry findings regarding ALS prevalence in the United States for the period January 1-December 31, 2015. In 2015, the estimated prevalence of ALS cases was 5.2 per 100,000 population with a total of 16,583 cases identified. Overall, these findings are similar to the 2014 ALS prevalence and case count (5.0 per 100,000; 15,927 cases) (2). Prevalence rates by patient characteristics (most common in whites, males, and persons aged ≥60 years) and U.S. Census regions are consistent with ALS demographics and have not changed from 2014 to 2015 calendar years. The algorithm used to identify cases from national administrative databases was updated from the International Classification of Diseases, Ninth Revision (ICD-9) to the ICD-10 codes for claims starting on October 1, 2015, with no apparent effect on case ascertainment. Data collected by the National ALS Registry are being used to better describe the epidemiology of ALS in the United States and to facilitate research on the genetics, potential biomarkers, environmental pollutants, and etiology for ALS.