Traditional vaccine development involves starting with the virus or pathogen and developing vaccines based on empirical evaluation. Most licensed vaccines currently fall within this category including whole-inactivated vaccines, live-attenuated vaccines that have been attenuated through passage methods, or proteins that have been purified from virus preparations, or produced in vitro using wild-type sequences. In contrast, rational vaccine design starts with knowledge of protective or presumably protective immune responses against a virus and designing vaccines to elicit that specific immune response. The recent shift towards rational vaccine designs has been enabled by the development of new technology. These transforming technologies include structure-based vaccine design, advances in sorting, sequencing and bioinformatics which enable a more in-depth analysis of immune responses, and rapid DNA synthesis which allows more rapid high-throughput evaluation of monoclonal antibodies and screening of antigens. Additionally, advances in gene editing have enhanced transgenic or humanized mouse models for vaccine evaluation and technologies for gene-based delivery of vaccine antigens have also improved. The development of these technologies has improved both the precision of vaccines by shifting the balance towards protective immune responses and away from non-protective responses, and the speed at which the immune response can be analyzed, and vaccines can be evaluated and manufactured. Rational vaccine design provides new solutions to old problems such as RSV and influenza, enables rapid response to emerging pathogens such as SARS-CoV2, and has the potential to improve vaccine safety for pathogens such as dengue virus.