To assess the current and future development of influenza vaccines. PubMed searches were performed cross-referencing the keywords influenza, influenza vaccine, host immune response, correlates of protection, vaccine development, vaccine efficacy. Articles were reviewed for additional citations. Articles were reviewed and selected on the basis of relevance to subject matter. In this review, we first introduce the influenza virus, its nomenclature, and the concepts of antigenic drift and shift. Second, we discuss the status of currently licensed influenza virus vaccines. We briefly focus on influenza vaccine responses beyond hemagglutination inhibition that may correlate with protection against influenza viruses of different subtypes. Third, we explain how studying host responses to influenza infection and vaccination with advanced serologic methods, B-cell receptor sequencing, and transcriptomic profiling can guide the development of improved influenza virus vaccines. Fourth, we provide 2 suggestions on how current influenza vaccines can be optimized by redirecting immune responses toward conserved viral antigens and the use of adjuvants. Influenza vaccine design can benefit from novel insights obtained from the study of host responses to influenza virus infection and vaccination. Integration of the large amount of available clinical and preclinical data requires systems approaches that can elucidate novel correlates of protection and will guide further development of influenza vaccine.