It has been challenging to develop an effective HIV vaccine but the lessons learned from HIV vaccine development will have broad impact to the future of translational medicine.The most important lesson is that results from basic research frequently did not predict the outcome of a pivotal clinical trial.After 30 years work,the heterologous prime-boost vaccination strategy is now recognized as a promising candidate platform which was completely unexpected even just a few years ago.The second lesson is that translational research is an iterative process and the correct next step can only be made after learning and careful analyzing the new knowledge learned from the previous step.