In 1993, I asked 150 leading HIV/AIDS researchers to list, in order of priority, the top 10 questions that needed to be answered to come up with a cure or, separately, a preventive vaccine. Science published the results as part of a special issue, AIDS: The Unanswered Questions, which came out on the eve of the infamous “doom and gloom” international conference in Berlin. My talk will revisit these questions, 15 years later, and look at whether they have been answered, in part or in full, or remain open. Along the way, I will review the dramatic progress the field has made and the daunting obstacles it still faces. I will also offer examples of treatment and prevention successes and failures from the many different countries I have visited to report on their HIV/AIDS epidemics.