A soil microbial community plays an important role in maintaining soil fertility and the efficiency of plant nutrient uptake. In plant rhizosphere region, various types of microbial interactions took place with soil nutrients and other pathogenic microbes. These groups of rhizosphere microbes include plant growth-promoting rhizobacteria (PGPR), mycorrhizal fungi, endophytic bacteria, biocontrol fungi, nitrogen-fixing symbiotic bacteria, and other beneficial microbial isolates. These groups directly contribute to the soil fertility and nutrient uptake profile of each geographic region. The current scenario of overuse of pesticides and chemical fertilizers has severely affected soil fertility and soil nutrient storage capacity. To maintain the fertility profile endowed with the resource-poor cultivation systems, the natural microbial activities can contribute to improved nutrient supply, better plant growth, biological control of pathogens, and maintenance of health of plant and production. In this chapter, we focus on understanding rhizosphere microbial interactions and their importance for sustainable farming systems in the future. In addition, the related factors affecting the quality and productivity of crops are briefly discussed.