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Abstract The rapid pace of industrial, agricultural and anthropogenic activities in the 20th century has resulted in contamination of heavy metals across the globe. Arsenic (As) is a ubiquitous, naturally occurring toxic metalloid, contaminating the soil and water and affecting human health in several countries. Several physicochemical methods exist for the cleanup of As contamination but these are expensive and disastrous to microbes and soil. Plant based remediation approaches are low cost and environmentally safe. Hence, extensive biochemical, molecular and genetic experiments have been conducted to understand plants’ responses to As stress and have led to the identification of potential genes. The available knowledge needs to be utilized to either reduce As accumulation in crop plants (rice) or to enhance As levels in shoots of hyperaccumulators (Pteris vittata). Gene manipulation using biotechnological tools can be an effective approach to exploit the potential genes (plasmamembrane and vacuolar transporters, glutathione and phytochelatin biosynthetic enzymes, etc.) playing pivotal roles in uptake, translocation, transformation, complexation, and compartmentalization of As in plants. The transgenic plants with increased tolerance to As and altered (increased/decreased) As accumulation have been developed. The need, however, exists to design plants with altered expression of two or more genes for harmonizing various events (like arsenate reduction, arsenite complexation, sequestration and translocation) so as to achieve desirable reduction (crop plants) or increase (phytoremediator plants) in As content. This review sheds light on transgenic approaches adopted to modulate As levels in plants and proposes future directions to achieve desirable results. Highlights • Arsenic is a toxic metalloid and a potential health hazard across the globe. • Arsenic stress responsive mechanisms and responsible crucial genes have been identified. • This review deals with the use of transgenic plants as an effective approach for arsenic removal. • The review also discusses the use of potential genes for lowering arsenic accumulation in crop plants. [ABSTRACT FROM AUTHOR]