African horse sickness (AHS) is a reportable, noncontagious, arthropod-borne viral disease that results in severe cardiovascular and pulmonary illness in horses. AHS is caused by the orbivirus African horse sickness virus (AHSV), which is transmitted primarily by Culicoides imicola in Africa; potential vectors outside of Africa include Culicoides variipennis and biting flies in the genera Stomoxys and Tabanus. Infection with AHSV has a high mortality rate. Quick and accurate diagnosis can help prevent the spread of AHS. AHS has not been reported in the Western Hemisphere but could have devastating consequences if introduced into the United States. This article reviews the clinical signs, pathologic changes, diagnostic challenges, and treatment options associated with AHS.