In 1963, Australian pathologist R.D.K. Reye first described this syndrome. National surveillance led to strict warnings regarding aspirin use in children. National surveillance of Reye syndrome in the U.S. began in 1973 when the U.S. Centers for Disease Control and Prevention (CDC) documented the first nationwide outbreak. Reye syndrome is a rare and potentially fatal pediatric illness defined as acute noninflammatory encephalopathy with fatty liver failure.

Fewer than 2 cases reported annually since 1994. However, the true incidence may not be known for reporting cases to the CDC is no longer mandated. Widespread warnings again the use of aspirin in children were issued in the U.S. in 1980. A sharp decline in the number of reported cases of Reye syndrome followed this issuance. Similar patterns of incidence were observed in the UK.