The intermittent outbreak of pandemic influenza and emergence of novel avian influenza A virus is worldwide threat. Although most patients present with mild symptoms, some deteriorate to severe pneumonia and even death. Great progress in the understanding of the mechanism of disease pathogenesis and a series of vaccines has been promoted worldwide; however, incidence, morbidity, and mortality remains high. To step up vigilance and improve pandemic preparedness, this article elucidates the virology, epidemiology, pathogenesis, clinical characteristics, and treatment of human infections by influenza A viruses, with an emphasis on the influenza A(H1N1)pdm09, H5N1, and H7N9 subtypes.