Results in 2012 from a Phase IIb efficacy trial of the CYD tetravalent dengue vaccine in the Ratchaburi province of Thailand, showed for the first time that a safe, efficacious vaccine against dengue is possible. It also raised questions on the reference PRNT assay methods, challenged some of the fundamental dengue vaccine development hypotheses, and served as a reminder of the complexity of dengue disease. Analyses have been carried out and are still ongoing to understand the main finding from the PhIIb study–that although efficacy was seen for 3 serotypes, none was seen for DENV2, despite satisfactory PRNT titers. These analyses included the sequencing of the clinical isolates from the PhIIb study, which, despite differences with the vaccine, were nevertheless cross neutralized in Vero cell-based in vitro assays In parallel, investigations continue to characterize vaccine-induced cellular responses: analyses from a trial in Singapore have confirmed the previous data showing the induction of broad serotype-specific Th1 responses dominated by IFNɣ;in addition, ongoing long-term follow up shows that cellular reponses persist for at least one year after vaccination. Assessment of safety remains a critical component of the dengue vaccine program. As of January 2013, more than 28900 have received one or more CYD-TDV vaccinations, with no safety signals identified in ongoing safety surveillance. A formal integrated safety analysis of 9 completed clinical trials with more than 5300 vaccinees confirms the good reactogenicity and safety profile seen in individual studies, including in the PhIIb study with 2 years of active follow-up. In the pivotal phase III efficacy trials, vaccinations have been completed and active surveillance is ongoing, and the drop out rate after 20 months is <5%. This low proportion attests to the considerable site preparation efforts by the local teams and the investigational teams’ commitment, and illustrates the importance of dengue disease for the communities. The results of these phase III trials are expected by the end of 2014.