Soil contamination poses long-term threats to living organisms and ecosystem. The unscientific use of agricultural chemicals, improper disposal of industrial effluents, and natural weathering of rocks have generated vast number of organic contaminants, heavy metals, and excessive salts in soil. The higher levels of these chemicals disrupt the health of land and aquatic life forms. The removal of these chemicals from the environment therefore presents a major challenge to us. Despite the use of many techniques in physical, chemical, and biological bioremediation efforts, researchers are in continuous search for greener, economic, and environmentally sustainable techniques. Although, phytoremediation solves many previously encountered challenges, still it is inefficient in large scale. Harnessing the interactions of hyperaccumulator plants with the plant growth-promoting microbes (microbe-assisted phytoremediation) can improve the phytoremediation potential. Therefore, understanding plant–microbial interactions and their mechanisms in removal or detoxification of soil contaminants holds the key for evolving better strategies. This chapter presents an overview of these interactions and mechanisms.