Pesticides are one of the three main contributors to poor water quality affecting the health and resilience of the Great Barrier Reef. Therefore, a program of monitoring pesticides in waterways that discharge to the Great Barrier Reef lagoon commenced in 2009. The program was initially limited in terms of the number of pesticides monitored and the number of waterways sampled. Since then, there has been continual and ongoing improvement and expansion of the program. Today it is not just a monitoring and reporting program but rather a comprehensive program that uses environmental chemistry and ecotoxicology to guide landscape scale change in pesticide use in approximately 424 000 km2 of agricultural land. Specifically, it aims to decrease the risk posed by pesticides to aquatic ecosystems. The development of the program will be briefly discussed before focussing on recent developments: a pesticide data portal; water quality guidelines for pesticides; ecologically relevant pesticide reduction targets, guideline exceedance notices; a method that utilises the multi-substance potentially affected fraction (msPAF) and the independent action model of joint toxicity to estimate the toxicity of mixtures of up to 22 commonly occurring pesticides; relationships that use proportional land use data to predict the toxicity of those mixtures; and a pesticide decision support tool that provides guidance to stakeholders on pesticides that are less harmful to aquatic organisms. The results generated by these components are helping guide stakeholders to change their practices and evaluate progress in reducing the pesticide risk at varying spatial scales from individual plots to the entire Great Barrier Reef catchment area. Finally, planned enhancements for the next three years that include developing guidelines for more pesticides, improving the land use relationships, spatially explicit predictions of pesticide mixture risk, and expanding the pesticide decision support tool will be discussed.