In the past when large investments have been made in tackling narrow scientific challenges, the enormous expansion in our knowledge in one small area has had a spill-over effect on research and treatment of other diseases. The large investment in HIV vaccine development in recent years has the potential for such an effect on vaccine development for other diseases. HIV vaccine developers have experienced repeated failure using the standard approaches to vaccine development. This has forced them to consider immune responses in greater depth and detail. It has led to a recognition of the importance of epitopic specificity in both antibody and T cell responses. Also, it has led to an understanding of the importance of affinity maturation in antibody responses and the quality of T cell responses in T cell-mediated immunity. It has advanced the development of many novel vaccine vectors and vehicles that are now available for use in other vaccines. Further, it has focused attention on the impact of research funding mechanisms and community engagement on vaccine development. These developments and considerations have implications for vaccinology more generally. Some suggestions are made for investigators working on other “hard-to-develop” vaccines.