This chapter briefly describes some examples of past and present (next to potential novel) applications of genetically modified micro-organisms to soil, stressing the importance of analysing the putative impacts of such applications to the life support functions (LSF) of a living soil at three levels: i) functioning for soil fertility; ii) functioning for pathogen suppressiveness; iii) functioning for the provision of clean drinking water. To understand the impact of such genetically modified micro-organism applications on the soil, it is important to deepen our understanding of the microbial communities that are responsible for the key LSF of that soil. Moreover, we need to understand how these might be affected mechanistically. It is, therefore, important to further develop databases that contain extensive data on the microbial communities in the soil systems under study. This chapter advocates the application of the currently available powerful methods, which enable the dissection of soil microbial systems into their individual components. Finally, the chapter proposes the definition of a normal operating range (NOR) to fit the dataset obtained into a framework which is quantifiable and may serve to support decision making.