The long-term and extensive use of insecticides has led to increasingly severe insecticide resistance, which has become a major challenge for both agriculture and public health. Significant progress has been made in recent years on understanding the molecular mechanisms responsible for insecticide resistance, particularly physiological resistance (including metabolic resistance and target-site resistance). This article summarizes both the current state and existing problems in research on the molecular mechanisms underlying insecticide resistance, and proposes directions for future research, including multi-resistance, resistance to RNA-based insecticides, high-throughput detection technologies, and the evolutionary patterns of resistance.