In the last 40 years, our knowledge of plant defense mechanisms against microbial colonization, as well as the effects of pathogens and symbionts on plant cells, has expanded greatly. However, as most molecular research has been conducted in sterile and controlled lab settings, we know relatively little about how environmental factors affect plant-microbe interactions at the mechanistic level. This chapter provides an overview of the many approaches utilized in the laboratory and at Insilco to study plant-microbe interactions. The spread of bacteria through the soil and their ability to penetrate normally impenetrable soil strata may be aided by plant roots. The effectiveness of phytoremediation and bio-augmentation might be greatly improved by inoculating plant seeds with pollutant-degrading bacteria. Additionally, system biology techniques may identify links that have eluded detection by other techniques or proteins, shedding light on their roles.