Stress shifts plant growth in nearly all species evident by developmental problems, such as decreased yield of dry matter and leaf area. However, few plants remain least affected or may nearly be remain unaffected. Primarily stress includes metal toxicity, a key source of abiotic stress influencing the health of plants. In general, metal toxification has been one of the major challenges in developmental processes. To combat this, remarkable number of plants have been recognized that have produced noteworthy effects in detoxification. In the current scenario, remediation focused on plants shows a growing potential against organic/inorganic polluted soils which is technically termed as “Phytoremediation.” Phytoremediation requires multiple methods for eliminating toxins from soil, in general through altered expression of genes and enzymes in plants. Few studies have also reported the application of plant-associated microbiota for decontamination polluted soils, sediments, and underground water and thus are currently being expanded as an ecologically sound and budget-friendly technology. Various latest advancements in recognizing plant cell/molecular processes of uptake/tolerance have also been well studied. New innovative molecular technologies have improved the perspective further into metabolic pathways involved in stress tolerance/prevention mechanisms in frequent cultivated crops and hyperaccumulator plants. The purpose of this chapter is to concentrate on the underlying molecular basis associated in detoxification and tolerance to contaminants by plants. In addition, the focus in this chapter is on the ability of “omics” and genetic modification strategies to effectively remediate a contaminated environment has also been described