This paper examines the intersection of the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) and the Endangered Species Act (ESA), focusing on the role of State Lead Agencies (SLAs) in implementing pesticide programs that comply with ESA requirements. It outlines the historical context of FIFRA and ESA integration, including the development of the Endangered Species Protection Program (ESPP) and the EPA’s ESA Workplan. The discussion emphasizes the importance of early SLA engagement in federal pesticide processes to ensure practical, enforceable mitigation measures for protecting listed species and critical habitats. Recommendations include improving communication, training, and enforcement strategies, as well as forming collaborative workgroups to address emerging compliance challenges. The paper concludes that SLAs are uniquely positioned to serve as conduits for local conditions and end-user perspectives, which are essential for successful implementation of ESA-related pesticide measures.