The practice of harvesting fish and crustaceans by using pesticides is understudied and under-reported in tropical inland fisheries yet poses a significant threat to freshwater biodiversity and community health. This research provides a brief review of the practice and an in-depth case study from southeast Nicaragua. In 2019, 86 interviews and 5 focus groups were conducted in remote communities in the Indio Maíz Biological Reserve (IMBR) and nearby surrounding area and combined with 4 years of local Indigenous Rama and Afrodescendent Kriol community forest ranger data. Forest rangers and 74% of interviewees reported that fishing with pesticides occurs in their communities, including both inside the IMBR and in the nearby surrounding area. The practice is primarily used by illegal settlers, and not by Rama and Kriol communities who have rights to the land in the IMBR. It entails the release of liquid pesticides in water or mixing powdered pesticides with corn flour and using the mixture as bait. Of seven chemicals reported, Cypermethrin, Deltamethrin, and Aluminum Phosphide were most common. The use of ichthyotoxic woody plants was more rarely reported. Habitats targeted ranged from swift headwaters to slow pools in small creeks to larger rivers, depending on target species. Main uses reported for the catch were food for family, bait to catch larger fish, and for sale. The main motivation was increased catch efficiency. Many interviewees attributed stomach issues, diarrhea, cough, convulsions, and miscarriage to exposure to poisoned river water. Twenty-five interviewees blamed poisoned rivers for livestock miscarriages or death. Severe local losses of fish and shrimp populations were reported. Rama and Kriol interviewees describe the practice as a threat to their river-based food security. Despite its illegality, no study participant knew a case of pesticide fishing that had been prosecuted. This destructive fishing practice has significant implications for conservation of the intact river systems of the primary rainforests of southeast Nicaragua, and to the local traditional fisheries they support.