The development of a vaccine that can prevent infection by the Human immunodeficiency virus or prevent the Acquired Immunodeficiency Syndrome has remained elusive despite 20 years of scientific effort. This "Commentary" analyzes the reasons that the development of a vaccine has been so difficult, and proposes a plan to work towards an immunological approach to investigate the best vaccine candidates in the first world in individuals who are already infected, before taking the most promising vaccines to the developing world to attempt to prevent infection and disease. SAGA: (Old Norse) "a long, continued heroic story that is action-packed, but not especially romantic, and that is historical or legendary or both".