When insects fight back: Mechanisms of insecticide resistance and strategies for sustainable pest control

Abstract Insecticides remain a primary tool for controlling agricultural pests and safeguarding crop productivity and public health. However, their widespread misuse has accelerated the evolution of resistance in many insect species, compromising the effectiveness of major insecticide classes and limiting available control options. This increasing challenge underscores the critical need for sustainable and innovative approaches to pest management. A thorough understanding of the fundamental causes and mechanisms of resistance is crucial for designing effective mitigation strategies. This review integrates current knowledge on insecticide resistance, with particular emphasis on metabolic detoxification mechanisms and target‐site insensitivity, as well as their interactions across a wide range of insect species. It examines the biochemical and molecular mechanisms driving resistance, the role of detoxification systems in insecticide metabolism and the potential of enzyme inhibitors, including commercially available compounds such as piperonyl butoxide (PBO), to counteract metabolic resistance. In addition, the review discusses common target‐site modifications associated with resistance to different insecticide classes and evaluates emerging molecular approaches, including RNA interference (RNAi) and CRISPR/Cas genome editing, as experimental tools with potential future applications in resistance monitoring and management. By integrating established and emerging strategies, this review provides a comprehensive framework to support the development of sustainable pest management programmes and identify key directions for future research aimed at mitigating insecticide resistance.