Dengue viruses cause more human morbidity and mortality than any other arthropod-borne virus. Dengue prevention relies primarily on vector control but the failure of traditional methods has promoted the development of novel entomological approaches. Although use of the intracellular bacterium Wolbachia to control mosquito populations was proposed half a century ago, it has only gained significant interest as a potential agent of dengue control in the last decade. Here, we review the evidence that supports a practical approach for dengue reduction through field release of Wolbachia-infected mosquitoes and discuss the additional studies that must be conducted before the strategy can be validated and operationally implemented. A critical next step is to assess the efficacy of Wolbachia deployment in reducing dengue virus transmission. We argue that a cluster-randomized trial is currently premature because Wolbachia strain choice for release as well as deployment strategies are still being optimized. We therefore present a pragmatic approach to acquiring preliminary evidence of efficacy via a suite of complementary methodologies: prospective cohort study, geographical cluster investigation, virus phylogenetic analysis, virus surveillance in mosquitoes, and vector competence assays. This multi-pronged approach could provide valuable intermediate evidence of efficacy to justify a future cluster-randomized trial.