The Center of Infectious Disease and Signaling Research (CIDSR) is a world-renowned research center which focuses on understanding how various agents including dengue virus, enteroviruses, hepatoma-associated viruses, and microbiota cause different human diseases. Some of these agents cause emerging and re-emerging infectious diseases which represent serious threats to humans in Taiwan and worldwide. Although surveillance and clinical care systems in Taiwan are well established, the potential for basic research and biotechnological capabilities have not yet been fully realized. National Cheng Kung University (NCKU) has a long and outstanding track record in infectious disease studies starting in 1996 with the establishment of the dengue research team on disease pathogenesis and protective strategies. Another pioneering group has been working on enterovirus A71 and providing clinical care since 1998. Furthermore, a research team has focused on hepatoma-associated viruses including hepatitis B virus and hepatitis C virus. In an effort to coordinate all of these outstanding research teams here at NCKU, The Center of Infectious Disease and Signaling Research was established in 2011 by Dr. Huan-Yao Lei. Drs. Wen-Chang Chang, Michael M. C. Lai, and Ih-Jen Su have served as members of the advisory committee. As a pioneer in dengue and enterovirus research and in efforts to address unmet needs of patient management, we have developed a range of novel diagnostic kits and found antivirals to help to identify individuals as candidates for therapeutic antibodies in order to decrease the morbidity of this disease. We have also established strong links with our international collaborators and hosted international conferences every year. International collaborations have greatly enhanced our success, including the quality of graduate student training, for example by involving international researchers on our MSc and PhD thesis committees. Together with our overseas collaborators, we will continue to develop novel therapies through innovative and cross-disciplinary research.