Heavy metals (HMs) contamination is one of the main among abiotic factors affecting crop productivity and also threatens human health via consuming metal contaminated crops as a food source. Over the past few years, HMs have drawn a lot of attention due to their increased use for commercial purposes and their harmful effects on plants and other life forms, thus threatening human survival. However, in recent years, several methods have been adopted to combat the harsh effects of HMs. After phytohormones, use of mineral nutrients such as selenium (Se) in the prevention of HM stress has been explored by the researchers more recently. Selenium is an important micronutrient widely known for its antioxidant properties in both plants and animals. Exogenous Se inhibits metal uptake and its translocation and also improves the antioxidant system, thus imparts resistance to HM toxicity in plants. Moreover, Se also regulates the production of various osmolytes in cells that helps in developing cell osmolarity. Selenium also induces the production of different types of secondary metabolites (SMs) that are also involved in plant's secondary defense mechanisms to different stresses. Uptake of mineral nutrients is a vital process for plant growth and development, which is also positively correlated with Se under metalloid toxicity. However, in order to understand the exact mechanism of Se in HM tolerance, different metabolic processes stimulated by Se and their pathways need to be explored. Hence, this review focuses on the role of Se on nutritional status, antioxidants metabolism, interaction with phytohormones and its role in the regulation of various genes involved in Se induced HM tolerance. Thus, this study will help researchers in the future for the improvement of HM tolerance via Se application in plants.