Hepatitis E virus (HEV), once thought to occur solely as an acute viral hepatitis in developing countries has gained much better understanding during the past decade. The variety of clinical presentations, ways of transmission and geographic distribution of the several HEV genotypes is much clearer these days, unveiling HEV’s true burden. As of today, potentially attributed to its zoonotic nature, HEV is considered endemic in many developed countries, as well as being the most common cause of acute viral hepatitis in some European countries. There are many more cases of cirrhosis and liver failure, once of unknown etiology, which are now attributed to chronic HEV infection in several patient settings, mostly with deficient immune system, often necessitating treatment. As the viral global disease burden is bigger than once thought, more focus is now being made on recognition, optimal treatment and prevention measures. This overview will focus on the current knowledge regarding HEV, and will cover the microbiological characteristics, epidemiology, pathogenesis, clinical course, and current practices in treatment and prophylaxis.