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Background: Phlebotomine sand flies are prominent vectors of Leishmania parasites that cause leishmaniasis, which comes second to malaria in terms of parasitic causative fatalities globally. In the absence of human vaccines, sand fly chemical-based vector control is a key component of leishmaniasis control efforts. Methods and findings: We performed a literature review on the current interventions, primarily, insecticide-based used for sand fly control, as well as the global insecticide resistance (IR) status of the main sand fly vector species. Indoor insecticidal interventions, such as residual spraying and treated bed nets are the most widely deployed, while several alternative control strategies are also used in certain settings and/or are under evaluation. IR has been sporadically detected in sand flies in India and other regions, using non-standardized diagnostic bioassays. Molecular studies are limited to monitoring of known pyrethroid resistance mutations (kdr), which are present at high frequencies in certain regions. Conclusions: As the leishmaniasis burden remains a major problem at a global scale, evidence-based rational use of insecticidal interventions is required to meet public health demands. Standardized bioassays and molecular markers are a prerequisite for this task, albeit are lagging behind. Experiences from other disease vectors underscore the need for the implementation of appropriate IR management (IRM) programs, in the framework of integrated vector management (IVM). The implementation of alternative strategies seems context- and case-specific, with key eco-epidemiological parameters yet to be investigated. New biotechnology-based control approaches might also come into play in the near future to further reinforce sand fly/leishmaniasis control efforts. Author summary: Phlebotomine sand flies, mainly aggregated in the tropics and subtropics, are prominent vectors Leishmania parasites that cause leishmaniasis, which comes second to malaria in terms of parasitic causative fatalities globally. In the absence of human vaccines, sand fly vector control is a key component of leishmaniasis prevention and control efforts. Here, we review the current methods and active ingredients applied for sand fly chemical control, as well as the IR data (bioassay and underlying mechanisms) available for dominant sand fly vector species worldwide. Future perspectives for improving the efficiency and sustainability of sand fly control applications, in the genomics era, including the use of molecular diagnostics for evidence-based IRM and the introduction of alternative biotechnology-based approaches, are discussed. [ABSTRACT FROM AUTHOR]