This overview examines recent progress in the application of molecular tools to the study of insect biology and the development of pest management strategies. The sequencing and annotation of insect genomes, coupled with analyses using comparative genomics, are providing new insights into the molecular underpinnings of insect-specific processes and shedding light on their evolutionary relationships. Researchers investigate the functions of insect genes using indirect approaches such as expression profiling, and direct methods such as insertional mutagenesis and RNA interference. Biotechnological applications to pest management include the development of resistant crops and trees that express insect-specific toxins, the design of microbial agents with enhanced insecticidal potency, and the engineering of insects that can transfer lethal genes to natural populations following their mass release in the field. Comparative genomics analyses also make it possible to identify insect-specific genes that can be targeted for rational insecticide design, using tools such as cell-based, high-throughput screening assays.