In late 2016, U.S. Embassy personnel in Havana, Cuba, began to report the development of an unusual set of symptoms and clinical signs. For some of these patients, their case began with the sudden onset of a loud noise, perceived to have directional features, and accompanied by pain in one or both ears or across a broad region of the head, and in some cases, a sensation of head pressure or vibration, dizziness, followed in some cases by tinnitus, visual problems, vertigo, and cognitive difficulties. Other personnel attached to the U.S. Consulate in Guangzhou, China, reported similar symptoms and signs to varying degrees, beginning in the following year. As of June 2020, many of these personnel continue to suffer from these and/or other health problems. Multiple hypotheses and mechanisms have been proposed to explain these clinical cases, but evidence has been lacking, no hypothesis has been proven, and the circumstances remain unclear. The Department of State asked the National Academies to review the cases, their clinical features and management, epidemiologic investigations, and scientific evidence in support of possible causes, and advise on approaches for the investigation of potential future cases. In An Assessment of Illness in U.S. Government Employees and Their Families at Overseas Embassies, the committee identifies distinctive clinical features, considers possible causes, evaluates plausible mechanisms and rehabilitation efforts, and offers recommendations for future planning and responses.