Juvenile hormone acid methyltransferase (JHAMT) catalyzes terminal methylation, which defines the structure of juvenile hormone (JH) and controls key processes in insect development, metamorphosis, reproduction, and polyphenism. Since its identification in the silkworm, Bombyx mori, in 2003, JHAMT has become central to elucidating the molecular basis of JH biosynthesis. Structural and biochemical studies have established a conserved SAM-dependent catalytic architecture and strict substrate specificity shared by insects and crustaceans. JHAMT expression is regulated by neural and hormonal cues, nutrient- and stress-responsive pathways, and CA-specific transcriptional and posttranscriptional mechanisms. Functional analyses using ribonucleic acid (RNA) interference (RNAi) and genome editing have demonstrated that JHAMT is indispensable for maintaining the larval state, coordinating metamorphic transitions, enabling fertility, and regulating diapause and other environmentally triggered phenotypes. Comparative genomics further revealed the strong conservation of canonical JHAMT orthologs and the extensive diversification of JHAMT-like paralogs. These insights highlight JHAMT as a key target for RNAi-based pest control, structure-guided inhibitor design, and metabolic engineering of sesquiterpenoid pathways, bridging fundamental insect endocrinology and applied biotechnological innovations.