This review focuses on the most important research topics that deal with issues that are currently being solved, those that remain unresolved, and future research directions. For the hepatitis A virus, we will address epidemiology, molecular surveillance, new susceptible populations, as well as environmental and food detections; for the hepatitis B virus, we will discuss host factors related to disease, diagnosis, therapy, and vaccine. Viral hepatitis, which is caused by infection with the hepatitis A, B, C, D, and E viruses, is a significant public health issue and a substantial cause of morbidity and mortality. As for the hepatitis D virus, we describe diagnostic methodology, pathogenesis, and therapy; for the hepatitis E virus, we will discuss epidemiology (including new emerging species), diagnosis, clinical aspects, treatment, vaccine development, and environmental surveillance; and for the hepatitis C virus, we will concentrate on pathogenesis, immunological response, direct action antiviral treatment in the context of solid organ transplantation, problems associated with the development of hepatocellular carcinoma, direct action antiviral resistance due to selection of resistance-associated variants and vaccination.