Hepatitis E is an acute, icteric, self-limiting disease, which is spread widely in many tropical and subtropical countries where it occurs both in the form of epidemics of variable magnitude or sporadically. Hepatitis E affects young adults, rather than children, and causes a high mortality rate, particularly in pregnant women. In industrialized countries this disease occurs occasionally as imported sporadic cases. The aetiological cause of hepatitis E is a virus, hepatitis E virus (HEV), which is temporally classified as a member of the Calicivirus family, although its genomic composition is unique. There are experimental data as well as epidemiological observations allowing us to assume that hepatitis E may be a zoonosis as HEV is pathogenic for some domestic and wild animals. Recently, serological assays based on the use of recombinant or synthetic antigens were developed and applied to determine the prevalence of antibody to HEV (anti-HEV) in various epidemic and non-epidemic settings. In suspected hepatitis E cases, anti-HEV seropositivity was detected at an elevated rate but the overall seroprevalence of anti-HEV in normal human populations of endemic areas appeared to be unexpectedly low. A low but constant presence of anti-HEV seropositivity was observed also in non-endemic industrialized countries. In some of these countries, anti-HEV seropositivity was accumulated in groups of patients with various liver and non-liver pathologies and certain groups at risk for blood-borne infections.