The history of influenza in Taiwan can be traced up to the 1918 H1N1 Spanish flu pandemic, followed by several others including the 1957 H2N2, 1968 H3N2, and the 2009 new H1N1. A couple of avian influenza viruses of H5N1 and H7N9 also posed threats to the general public in Taiwan in the two recent decades. Nevertheless, two seasonal influenza A viruses and two lineages of influenza B viruses continue causing annual endemics one after the other, or appearing simultaneously. Their interplay provided interesting evolutionary trajectories for these viruses, allowing us to computationally model their global migrations together with the data collected elsewhere from different geographical locations. An island-wide laboratory-based surveillance network was also established since 2000 for systematically collecting and managing the disease and molecular epidemiology. Experiences learned from this network helped in encountering and managing newly emerging infectious diseases, including the 2003 SARS and 2009 H1N1 outbreaks.