An effective HIV vaccine is a global health priority. The Merck Ad5 phase IIb T-cell vaccine failed to show efficacy and might have increased the risk of HIV acquisition in MSM. While VaxGen gp120 alone was not efficacious in groups at high risk for HIV-1 infection, the RV144 ALVAC-HIV prime and AIDSVAX gp120 B/E boost regimen showed 31% efficacy in low incidence heterosexuals in Thailand. All trials demonstrated the limitations of available laboratory and animal models to both assess relevant vaccine-induced immune responses and to predict clinical trial outcome. We have begun an intensive, broad based attempt to discover a correlate of protection from RV 144 involving over 30 investigators at 20 institutions examining the innate and adaptive responses induced in RV 144, viral sieve and host genetic studies, and non-human primate studies. Results of some of these studies will be described. A roadmap for future HIV vaccine trials will be described designed to better define RV 144 correlates of protection, improve the durability and level of protection observed, and assess protective vaccine efficacy in diverse risk groups. New strategies examining heterologous vector prime boost, universal inserts, replicating vectors, and novel protein/adjuvant immunogens should be explored to induce both T-cell and antibody responses. These new approaches will be described within the context of the roadmap for future HIV vaccine efficacy studies. HIV vaccine development requires innovative ideas and a sustained long-term commitment of scientists, governments, and the community.