168Metalloids are the group of elements that have physical and chemical properties in between metals and nonmetals. This group consists of arsenic (As), boron (B), silicon (Si), germanium (Ge), antimony (Sb), and tellurium (Te). Certain other elements, such as selenium (Se), are sometimes added to the list of metalloids. Arsenic, boron, selenium and antimony are known to cause toxicity in plants at higher concentrations. Natural occurrence and anthropogenic activities have led to widespread contamination of these metalloids in many parts of the world. Plants growing in these areas are exposed to various forms of metalloid species depending on the redox potential and pH of the soil. Toxic metalloid species cause yield reduction in crops. Moreover, consumption of these contaminated crops exposes a large section of the human population to potential metalloid poisoning. Thus, developing metalloid tolerance and reducing its concentration in edible parts of crops are of critical importance. A thorough molecular understanding of the mechanisms of metalloid uptake, transport, toxicity, and tolerance in plants will help in development of metalloid tolerant and safe plants that can sequester metalloids in non-edible plant tissues. Significant advancement has been made in the identification and characterization of genes and proteins responsible for uptake, movement and tolerance of metalloids within plants. In this chapter, we provide an overview of these findings and their application in development of transgenic plants with enhanced metalloid tolerance and ability to restrict metalloids in non-edible plant parts.