Arsenic (As) is a nonessential and toxic element to all forms of life. It exists naturally at high concentrations in the soil and water of some regions of the world, predominantly in Southeast Asia. The use of As-tainted groundwater for irrigation purposes is becoming a serious hazard, causing phytotoxicity to crop plants due to high As accumulation, which poses food chain contamination and health risk to humans. A number of transcriptomic, proteomic, and metabolomic studies have been conducted to unravel the mechanisms responsible for As toxicity and tolerance in plants. The outcome of these studies in the form of mechanistic details of As–plant interaction would be useful in the development of low As accumulating crop plants by maintaining the cellular and genetic veracity of plants in future. This chapter aims to discuss up-to-date knowledge of plant As uptake, speciation, and transport, along with involvement of genetic changes during As stress.