Pollution due to the industrialization has increased enormously, especially in the developing countries. Different reliable approaches are being used in the remediation of organic and inorganic contaminants. Microbe-mediated phytoremediation is considered as apotential approach for the treatment of mixed pollutants. Studies have reported that microbes, including bacteria and fungi, exhibit beneficial role in growth promotion, stress alleviation, and degradation. Further, microbes help plant species to survive under higher concentrations of pollutants in the soil. Microbes induce various innate plant growth promoting traits, including phytohormone production, siderophores, and chelating substances, thereby indirectly play a role in the bioremediation and microbe-mediated removal of various pollutants. These microbes mobilize the pollutants in the rhizosphere region of plants, which are then taken up by plants. They also help plants to resist against various environmental stresses. Plants, in turn, release the exudates and enzymes that stimulate biochemical and microbial activities in the adjoining soil, thus supporting the bioremediation. The challenge in future for the expansion of the microbe-based phytoremediation is to develop efficient tools for their credibility in predicting their effectiveness in restoration of contaminated sites. The current chapter highlights the specific role of microbes in assisting phytoremediation and challenges associated with plant-microbe interactions.