Environmental pollution is one the major problems that affects biodiversity, ecosystems, and human health worldwide by contaminating soil and water. This issue cannot be resolved through conventional tools and traditional strategies. The in-depth understanding of biotechnological interventions with the prospect to upgrade the phytoremediation potential needs to be elucidated. Plants deploy multiple physiological, biochemical, and molecular mechanisms to counter the deleterious effects of environmental pollutants. Phytoremediation, the use of plants for environmental restoration, exploits naturally occurring uptake capabilities of plant root systems, together with the translocation, bioaccumulation, or detoxifying abilities to clean up the surrounding environments. Phytoremediation is a cost-effective, environmentally friendly, nonintrusive, and affordable technological solution used to extract or remove inactive metals and metal pollutants from contaminated soil and water. Recent technological development of molecular genetics and transgenic approaches has significantly increased the understanding of mechanisms of phytoremediation and recent results including the overexpression of genes engaged with metal uptake, transport, and sequestration of enzymes engaged with degradation of hazardous organic compounds have opened up new possibilities of phytoremediation. This chapter provides a critical review of the recent progress made toward the development of transgenic plants with improved phytoremediation capabilities and their potential use in environmental cleanup.