Since the identification of HIV in 1984, the search for a safe and effective vaccine has been relentless. While investigator-initiated research has provided substantial information regarding HIV disease and pathogenesis, and over two dozen drugs are licensed in the USA to treat HIV, the global epidemic continues unabated. Early in HIV vaccine research, the pharmaceutical industry took the initiative to produce products for clinical testing. As the likelihood of a quick success decreased, private investment waned. The public sector responded with novel mechanisms to engage industry while continuing to support academic investigators. HIV vaccine research continues to rely on the creativity of individual investigators, as well as collaborations that vary in size and complexity and offer opportunities for the efficient use of resources and accelerated progress.