Microorganisms in soil regulate a wide range of processes that are critical for plant growth and crop productivity. A large, diverse and active soil biota could help provide soil conditions for sustainable cotton production through (i) crop residue decomposition and improvement of nutrient supplying potential of soils, (ii) preventing aggressive plant pathogens taking hold and improve plants ability to withstand disease effects, (iii) reducing the loss of inorganic fertilizers through erosion and leaching by short-term immobilization (iv) stabilizing soil structure and (v) reducing the reliance for agrochemicals and reduced persistence of pesticides in soil and thus less off-site impacts. In a high input cropping systems such as cotton, it is essential to maintain activities of key microbial groups to maximize input efficiency and to reduce non-target environmental negative effects.