Bacillus thuringiensis subsp. israelensis (Bti) is the most widely used biological larvicide for mosquito control worldwide and a cornerstone of environmentally sustainable vector-management programs. Its long-term global deployment reflects a well-characterized balance between public-health benefit and manageable ecological tradeoffs within integrated vector management (IVM) frameworks. Bti combines high larvicidal efficacy, operational simplicity, and strong target specificity, resulting in an exceptional safety profile for humans and vertebrate wildlife. Decades of laboratory and field studies demonstrate that Bti is biologically selective rather than ecologically inert, with reproducible yet context-dependent effects confined to closely related non-target aquatic dipterans. This review links the molecular and toxicological foundations of Bti to its operational performance, ecological selectivity, resistance-mitigating properties, and sustained utility in mosquito-control programs. Beyond its established larvicidal function, Bti’s prokaryotic insect larvicidal organelle (PILO) represents an underexplored platform for heterologous intracellular protein assembly. Its dense packing, structural stability, and resistance to environmental and biochemical stress indicate an evolutionary specialization for high-capacity protein storage during sporulation. These properties support noncanonical applications in biomolecule storage and stabilization and motivate cautious exploration of environmentally responsive protein release strategies. Although significant mechanistic and translational challenges remain, particularly with respect to cargo trafficking, modularity, and purification, the architectural principles that have enabled effective mosquito control provide a strong foundation for extending PILO-based platforms beyond larvicidal applications.