Acute viral hepatitis is a systemic infection that affects predominantly the liver and remains a significant cause of morbidity and mortality in the United States despite the availability of effective vaccination against hepatitis A and B, the two major causes of viral hepatitis. There are five major hepatotropic viruses (A, B, C, D, and E) that cause acute hepatitis, resulting in acute hepatic necrosis and inflammation. Acute viral hepatitis typically runs its course in 6 months or less, in contrast to chronic hepatitis, which persists for longer. However, with modern serological and molecular diagnostic testing, the time course is less important in distinguishing acute from chronic viral hepatitis. The clinical illness produced by these viruses can range from asymptomatic and clinically inapparent to a fulminant and fatal acute infection. A major distinction between hepatitis A and E compared to hepatitis B, C, and D is that the former cause acute hepatitis only in contrast to the latter three, which are also important causes of chronic hepatitis and cirrhosis. Other viral infections, such as Epstein–Barr virus (EBV) and cytomegalovirus (CMV), can present with prominent hepatic dysfunction, although they are usually multisystem disorders. Hepatitis G virus and TT virus (TTV) have also been implicated in causing hepatic dysfunction, but their clinical significance remains dubious.