Viral hepatitis (VH) is almost as old as human beings, at least as old as known human history. However, the natural history and the epidemiology of the disease has undergone changes during the centuries and even recently we have been facing several new aspects. The estimated global prevalence is around 3-5%, which means that approximately 400 million patients are infected with hepatitis B virus and that there are 170 million infections with hepatitis C virus. The mortality figures are projected to show a 2- to 3-fold increase over the next two decades as hepatitis C virus-infected patients develop cirrhosis, which makes this the leading indication for liver transplantation. These data point to the importance of VH being a significant public health problem worldwide. The list of hepatotropic viruses is well known, including hepatitis A (HAV), B (HBV), C (HCV), D (HDV), E (HEV), G (HGV) and F (HFV). HGV and HFV are excluded from the present review, mainly because they are questionable in relation to the causation of liver disease. Our knowledge of HAV, HBV, HDV and HEV has accumulated over the last decade, so the present discussion is focused on HCV, which is currently generating considerable concern and controversy, and is the leading cause of chronic liver disease worldwide. The main questions to be discussed, are: the characterization of the agents' viral genotypes/subtypes, the viral-cell interaction, the pathogenesis of VH, the extrahepatic manifestations of viral infection and hepatocarcinogenesis.