Hepatitis E is attributed great attention as an emerging worldwide-distributed zoonosis. The clinical presentation varies from severe fulminant in underdeveloped to milder forms of diagnostically unrecognized hepatitis cases in developed countries. Chronic hepatitis E is more often described in subjects with transplanted solid organs and HIV disease. The diagnosis of hepatitis E is established by determination of anti-HEV IgM and IgG with Western blot confirmation and detection of HEV RNA. In Croatia, the first case of indigenous disease caused by HEV genotype 3 (HEV-3) was detected in 2012. In this paper we present current knowledge on hepatitis E supplemented by own results obtained at the University Hospital for Infectious Diseases in Zagreb and guidelines for diagnosis and treatment of immunocompetent and immunocompromised individuals. In the period from 2011-2014, HEV was tested in 1107 patients, of whom 117 (10.6%) had anti-HEV antibodies. Acute HEV infection was diagnosed in 25 (2.3%) patients. Considering the prevalence of antibodies we can conclude that HEV diagnostics should be included in the diagnostic panel for patients with elevated aminotransferases.