This chapter explores the biological and virological foundations of silkworm biotechnology, beginning with an overview of the silkworm (Bombyx mori) life cycle and the historical impact of infectious diseases on the global silk industry. It provides a detailed examination of baculoviruses, particularly Autographa californica multiple nucleopolyhedrovirus (AcMNPV) and Bombyx mori nucleopolyhedrovirus (BmNPV). The chapter delineates the biphasic baculovirus life cycle, highlighting the distinct roles of budded viruses (BVs) for systemic propagation within the host and occlusion-derived viruses (ODVs) for robust inter-host transmission. Furthermore, it analyzes the genomic organization of these large, double-stranded DNA viruses. Despite sharing over 90% sequence homology, AcMNPV and BmNPV exhibit strict host specificities, which are primarily governed by the viral DNA helicase gene (p143). By elucidating the molecular mechanisms of viral replication, host-range determination, and viral-induced host liquefaction (mediated by enzymes like chitinase and cathepsin), this chapter establishes the critical virological principles that enabled the transformation of pathogenic baculoviruses into powerful expression vectors for modern biotechnology.