Technical Abstract: The biotechnological revolution has forever changed agricultural research and crop production worldwide. Commercial agriculture now includes plants that produce enhanced yield and quality, survival in hostile environmental conditions, manufacture and express defensive toxins, and yield grains with greatly enhanced nutrient fortification. Unprecedented opportunities and ethical challenges created by this new technology are transforming the field of plant protection may be compared with the dramatic changes of an insect undergoes during metamorphosis. In particular, the technology has brought enormous exciting opportunities as well as great challenges that are transforming the research fields of innate (or cisgenic) insect resistance and insect-host plant interactions. Here, we provide a review of the historic milestones in both cisgenic (insertion of genes from sexually compatible stock) and transgenic (insertion of genes from sexually incompatible stock) crop production in agriculture. Biological significance of transgenic technology and the critical role of basic research in crop and human protection are discussed. In addition, three research frontiers that utilize basic and applied research approaches and synergistically combine cisgenes with transgenic technology for broad crop protection (including both yield and quality improvements) are also discussed.