Ralf Bartenschlager is a molecular and cell biologist by training and interested in the complexities of the interactions between viruses and their host cells. He studied at the University of Heidelberg in Germany and moved as postdoctoral fellow to a major pharmaceutical company to establish a research program on hepatitis C virus. In 1994, Bartenschlager joined back academia and established his own research group within the newly founded institute of virology at the University of Mainz in Germany. In 2003 he moved back to Heidelberg to establish the Chica & Heinz Schaller endowed professorship for Molecular Virology within the Department of Infectious Diseases at Heidelberg University Clinic. The main research interests of Ralf Bartenschlager center on hepatitis viruses. Having revealed some basic features of the replication cycle of the hepatitis B virus (HBV) during his PhD studies, he joined the hepatitis C virus (HCV) research field that emerged as a result of the discovery of this virus in 1989. A major topic in the Bartenschlager lab was the characterization of HCV enzymes suitable as targets for antiviral drugs and the development of a cell culture system for this virus, which he was able to establish, together with his colleague Volker Lohmann, in 1999. This system that was based on engineered HCV mini-genomes, along with the extensive characterization of the viral NS3 protease and the NS5B polymerase, laid the ground for the development of antiviral drugs that are in clinical use and allow virus elimination in >95% of treated patients. More recent work in the Bartenschlager lab centers on the strategies used by HCV and HBV to establish persistence. These studies are conducted in a transregional collaborative research center (TRR179), coordinated by Bartenschlager, where HCV is used as a unique model system to study how the elimination of a virus impacts the reconstitution of innate and adaptive immune responses in infected patients. Other research directions relate to the mode-of-action of NS5A inhibitors that are a cornerstone of therapy of chronic hepatitis C, the development of candidate antigens suitable for a prophylactic vaccine and to unveil the mechanisms underlying HCV-associated liver cancer. More recently, the Bartenschlager group started working on the molecular and cell biology of flaviviruses, notably Dengue virus and Zika virus. Infections with these viruses pose a major medical burden, yet antiviral therapy is not available. For that reason, knowledge gained from these basic research studies will be used to define possible targets for novel broad-spectrum antiviral drugs, suitable to treat infections with these flaviviruses. Finally, the Bartenschlager group has developed new bioinformatics tools to search for yet unknown viruses. By using the approach, it could be shown that HBV-related viruses existed more than 430 million years ago arguing for a long-term co-evolution of these viruses, including HBV, with their hosts. Currently, these search algorithms are employed to identify novel viruses and to decipher their evolutionary traits.