Every May, GASTROENTEROLOGY publishes a supplementary issue, the “13th Issue”, that is devoted to a specific topic or theme. When the 2012 theme was discussed by the new Board of Editors (each member of which desperately tried to avoid having his or her favorite topic be chosen, as this would undoubtedly mean a considerable amount of additional work), the topic of viral hepatitis emerged unanimously. It must be acknowledged that no other field in Hepatology and Gastroenterology has grown more rapidly than viral hepatitis during the past 15 years, thanks to the considerable interest of the scientific community for diseases that involve over 500 million patients worldwide, active support for research from governments in the United States, Europe, Japan, and Australia, among other regions, and major drug industry investment for what promises to be an incredibly rewarding market for antiviral drugs. Viral hepatitis care and research are now at a crossroad. After many years of investigation aimed at understanding the life cycle of hepatitis viruses, the immunology of acute and chronic infection and the pathophysiology of related liver and extra-hepatic disorders, the field is poised with powerful therapeutic and preventive strategies that will efficiently control these infections. With entecavir and tenofovir now approved in most areas of the world, hepatitis B virus (HBV) replication can be controlled in the long-term in the vast majority of chronically infected patients. In addition, the universal HBV vaccination of newborns in high endemic areas has proven to reduce not only HBV infection but also HBV-related hepatocellular carcinoma (HCC). After some false starts, the search for antiviral drugs targeting hepatitis C virus (HCV) is now moving at an incredible pace with more than 100 compounds currently at the preclinical, or early-to-late clinical developmental stages. After 10 years of stagnation with pegylated interferon alfa and ribavirin therapy, 2 specific inhibitors of the HCV NS3/4A protease, telaprevir and boceprevir, were approved in 2011 in the United States and Europe for the treatment of patients infected with HCV genotype 1. Many other compounds are likely to be approved within the next 5 years. Most importantly, the hope that very high rates of viral eradication will be achieved soon with all-oral, interferon-free regimens is no longer a fantasy. Reasonably, one can now foresee that most chronic HCV infections will be cured, at least in countries that will be able to afford the high price of the new drug combinations. In such a context, priorities are rapidly changing in viral hepatitis research, as new issues arise and new challenges emerge. Our goals in this special issue of GASTROENTEROLOGY were to give the readers an up-to-date insight into the tremendous progress made over the past few years in viral hepatitis research and care, and to guide them through complex challenges and expected future developments with the help of an outstanding group of thoughtful expert international leaders. Thus, this issue not only contains classical review articles dealing with important areas in which major advances have occurred recently, but also includes editorial-like commentaries exploring critical unresolved issues and fundamental questions for the future. The 2012 special issue, which is mainly related to HBV and HCV infections, has been divided into 4 sections: section 1 deals with epidemiology and pathophysiology; section 2 with diagnostic and prognostic tools; and section 3 with therapy and prevention. Section 4 includes an article discussing hepatitis E virus (HEV), a neglected virus that was recently found to be of clinical importance in industrialized countries. In the first section, devoted to epidemiology and pathophysiology, Dr Hashem B. El-Serag (pages 1264 –1273) carefully reviews the epidemiology of HCC in relation to viral hepatitis.1 He clearly demonstrates the primary role