Half a decade after the contentious “gain-of-function” (GOF) debate of 2012 that followed experimentation showing that highly pathogenic avian influenza virus could become mammalian transmissible, it is possible to reflect on the arguments for and against this type of research. In this essay we argue that GOF-type experiments have already produced important information not available from any other source while also providing information on pathogenesis and the requirements for optimizing strains for vaccine production. We analyze the moral arguments against GOF and find them less compelling for a variety of reasons ranging from the uncertainty of risk-benefit analysis to the reduced likelihood of accidents given the enhanced biosafety and biosecurity protocols currently in place. In our view the most important consequence of the GOF debate is that it brought renewed attention to biosafety protocols and ushered innovation in answering the relevant biological questions with greater safety. We conclude that GOF experiments should go forward provided that necessary biosafety and biosecurity conditions are in place.